Devices and methods for delivering dry powder medicaments

ABSTRACT

An apparatus includes a first member coupled to a second member. The first member defines a chamber containing a dry powder and includes a chamber wall that forms an outer boundary of the chamber. The second member includes a surface covering the chamber and defines an intake channel and an exit channel The exit channel is fluidically coupled to the chamber via an exit opening. The intake channel is fluidically coupled to the chamber via an intake port. A center line of the intake channel is tangential to a portion of the chamber wall such that a portion of an inlet airflow conveyed into the chamber via the intake channel has a rotational motion. The intake port is defined at least in part by an intake ramp. The intake ramp includes a transition surface that forms an exit angle with respect to the surface of less than 105 degrees.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit of priority to U.S. ProvisionalApplication Ser. No. 62/477,506, entitled “Devices and Methods forDelivering Dry Powder Medicaments,” filed Mar. 28, 2017, which isincorporated herein by reference in its entirety.

BACKGROUND

The embodiments described herein relate generally to medical devices andpharmaceutical compositions, and more particularly to drug products fordelivery of dry powder medicaments.

Pressurized metered dose inhalation devices (pMDI) are well-known fordelivering drugs to patients by way of their lungs. pMDI's are comprisedof a pressurized propellant canister with a metering valve housed in amolded actuator body with integral mouthpiece. This type of inhalationdevice presents drug delivery challenges to patients, requiringsignificant force to actuate with inhalation and timing coordination toeffectively receive the drug. pMDI's containing suspended drugformulations also have to be shaken properly by the patient prior toactuating to receive an effective dose of the drug. These relativelycomplicated devices also require priming due to low drug content ininitial doses and can require cleaning by the patient. In some devices,an additional spacer apparatus is prescribed along with the pMDI tocompensate for the timing coordination issue, thus creating additionalcomplications related to the patient for, cleaning, storage andtransport of the bulky spacer apparatus. While many patients areexperienced operating pMDI's or pMDI's with spacers, new patients oftenexperience a relatively significant learning curve to operate thesedevices properly.

Dry powder inhalation devices (DPI) are also well-known for deliveringpowderized drugs to the lungs. DPI technologies are either activeinvolving external energy to break-up and aerosolize particles or,passive utilizing the patient's inspiratory energy to entrain anddeliver the powder to the lungs. Some DPI technologies integrateelectronics while others are fully mechanical. The powder drug storageformats are normally reservoir, individually pre-metered doses, orcapsule based systems. Some known DPI devices include (or deliver)engineered drug particles, but in most known devices deliver aconventional blend of sized active pharmaceutical ingredient(s) (API)plus sized lactose monohydrate used as a bulking agent to aid in thepowder filling process and as carrier particles to aid in delivery ofthe active pharmaceutical ingredient(s) to the patient. TheseAPI—lactose monohydrate blends among others require a means to break-upaggregates formed by attractive forces holding them together.

Some known devices for storing and delivering known dry powderformulations include a storage reservoir and a separate chamber withinwhich the dry powder can be disaggregated in preparation for delivery tothe patient. Such known systems, however, often include multiplepathways (e.g., from the reservoir to the preparation chamber), and thuscan have diminished accuracy of the delivered dose due to undesiredcontact with pathway walls, inconsistency in withdrawing the dose fromthe reservoir, and the like.

Some known devices for storing and delivering known dry powderformulations rely, at least in part, on air flow produced by the patientinspiration (i.e., inhalation). Variation in the flow rates andvelocities produced among the patient population, however, can causevariation in the delivered dose and/or fine particle fraction. Moreover,normal part-to-part variation, as well as variation caused during use(e.g., deformation or blocking of flow paths due to the patient grippingthe device) can also lead to undesired variation in the airflowresistance and accuracy of the delivered dose, as well as the magnitudeof fine particle fraction.

Additionally, some known dry powder delivery devices are susceptible toinconsistent performance resulting from variations in how differentusers interact with the device. Said another way, known dry powderdelivery devices do not account for “human factors” in operation. Forexample, known dry powder delivery devices can be susceptible tovariations in performance based on any one or all the following: tiltingof the device (before or during use), failure to generate adequate flowand pressure drop (vacuum or negative pressure), failure by the user toactuate mechanisms completely and properly (and in the correct order),and failure to load drug cartridges, capsules or blisters properly. Asone example, some known dry powder delivery devices include passagewaysthat can be obstructed if a user inadvertently covers an inlet port orsqueezes the body of the device with too much force.

Thus, a need exists for improved methods and devices for delivering drypowder drugs. Specifically, a need exists for a dry powder deliverydevice having improved accuracy, improved fine particle fraction, andease of use and administration. A need also exists for improved methodsof filling and assembling dry powder delivery devices.

SUMMARY

Medicament delivery devices, drug products and methods foradministration of dry powder medicaments are described herein. In someembodiments, an apparatus includes a first member and a second membercoupled to the first member. The first member defines at least a portionof a disaggregation chamber containing a dry powder and includes achamber wall that forms an outer boundary of the disaggregation chamber.The second member includes a surface covering the disaggregation chamberand defines an intake channel and an exit channel. The exit channel isconfigured to be fluidically coupled to the disaggregation chamber viaan exit opening defined by the surface of the second member. The intakechannel is configured to be fluidically coupled to the disaggregationchamber via an intake port. A center line of a portion of the intakechannel is tangential to a portion of the chamber wall of the firstmember such that a portion of an inlet airflow conveyed into thedisaggregation chamber via the intake channel has a rotational motionabout a center axis of the disaggregation chamber. The intake port isdefined at least in part by an intake ramp. The intake ramp includes atransition surface that forms an exit angle with respect to the surfaceof less than 105 degrees.

In some embodiments, an apparatus includes a lower member and an uppermember coupled to the lower member. The lower member defines at least alower portion of a disaggregation chamber containing a dry powder. Thelower member includes a raised surface along a center axis of thedisaggregation chamber. The upper member includes a surface thatencloses the disaggregation chamber and defines an upper portion of thedisaggregation chamber, the upper member defines an intake channel andan exit channel. The intake channel is fluidically coupled to thedisaggregation chamber via an intake opening, and the exit channel isfluidically coupled to the disaggregation chamber via an exit openingdefined by the surface of the upper member. The exit opening is alongthe center axis. The upper member includes a protrusion extending fromthe surface, the protrusion in contact with the raised surface tomaintain a distance between the raised surface and the exit opening.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 are schematic illustrations of a medicament deliverydevice, according to an embodiment, in various stages of operation.

FIG. 3 is a cross-section view of a portion of the medicament deliverydevice shown in FIG. 1 taken along line X-X.

FIGS. 4, 5, and 7 are schematic illustrations of a medicament deliverydevice, according to an embodiment, in various stages of operation.

FIG. 6 is a cross-section view of a portion of the medicament deliverydevice shown in FIG. 4 taken along line X-X.

FIG. 8 is a schematic illustration of a medicament delivery device,according to an embodiment.

FIGS. 9 and 10 are perspective views of a first side of a medicamentdelivery device, according to an embodiment.

FIG. 11 is a top view of the medicament delivery device shown in FIGS. 9and 10, in an opened configuration.

FIG. 12 is a cross-sectional view of the medicament delivery deviceshown in FIG. 11 taken along line A1-A1.

FIG. 13 is a perspective view of a second side of the medicamentdelivery device shown in FIGS. 9 and 10.

FIG. 14 is a top view of an upper portion of the medicament deliverydevice shown in FIGS. 9-13.

FIGS. 15 and 16 are cross-sectional views of the upper portion of themedicament delivery device shown in FIGS. 9-13, taken along lines X₁-X₁and X₂-X₂, respectively.

FIG. 17 is a perspective view of the upper portion of the medicamentdelivery device shown in FIGS. 9-13.

FIG. 18 is an exploded view of the medicament delivery device shown inFIGS. 9-13, in an opened configuration, showing a strip.

FIG. 19 is a perspective view of the medicament delivery device shown inFIGS. 9-13, in an opened configuration, with the strip coupled to thefirst member.

FIG. 20 is a perspective view of the medicament delivery device shown inFIGS. 9-13, being moved from an opened configuration to a closedconfiguration.

FIG. 21 is a perspective view of the medicament delivery device shown inFIGS. 9-13, in a closed configuration, with the strip in place.

FIG. 22 is a perspective view of the medicament delivery device shown inFIGS. 9-13, in a closed configuration, with the strip removed.

FIG. 23 is an enlarged view of a portion of the medicament deliverydevice shown in FIG. 22 identified by the region Z in FIG. 22.

FIG. 24 is a perspective cross-sectional view of the medicament deliverydevice shown in FIGS. 9-13, in a closed configuration, with the strip inplace.

FIG. 25 is a top view of the medicament delivery device shown in FIGS.9-13, in a closed configuration, with the strip in place.

FIG. 26A is a top view of the medicament delivery device shown in FIGS.9-13, in a closed configuration, with the strip removed.

FIGS. 26B and 26C are cross-sectional views of the medicament deliverydevice shown in FIG. 26A taken along line A1-A1 (FIG. 26B) and A2-A2(FIG. 26C).

FIG. 27 is an enlarged view of a portion of the medicament deliverydevice shown in FIG. 26B identified by the region Z in FIG. 26B.

FIG. 28 is a top view of a lower portion of the medicament deliverydevice shown in FIGS. 9-13, showing an airflow pattern.

FIG. 29 is a top view of the medicament delivery device shown in FIGS.9-13, in the closed configuration, showing an airflow pattern.

FIG. 30 is a flow chart of a method of delivering a medicament,according to an embodiment.

FIG. 31 is a flow chart of a method of assembling a medicament deliverydevice, according to an embodiment.

FIG. 32A is a top view of a medicament delivery device, according to anembodiment, in a closed configuration.

FIG. 32B is a cross-sectional view of the medicament delivery deviceshown in FIG. 32A taken along line A1-A1.

FIG. 33 is an enlarged view of a portion of the medicament deliverydevice shown in FIG. 32B identified by the region Z in FIG. 32B.

FIG. 34 is an enlarged cross-sectional view of a portion of a medicamentdelivery device, according to an embodiment, in a closed configuration.

FIGS. 35A-35C are top views of various medicament delivery devicesaccording to various embodiments, each having a different inlet airpassageway geometry and flow characteristics.

FIG. 36 is a top view of an upper portion of a medicament deliverydevice, according to an embodiment.

FIG. 37 is a perspective view of a portion of the medicament deliverydevice shown in FIG. 36.

FIG. 38 is a bottom view of an upper portion of a medicament deliverydevice, according to an embodiment.

FIG. 39 is a top view of a portion of a medicament delivery device in anopened configuration, according to an embodiment.

FIG. 40 is a top view of a portion of the medicament delivery deviceshown in FIG. 39 in a closed configuration.

FIG. 41 is a top view of a portion of a medicament delivery device,according to an embodiment.

FIG. 42 is a top view of a portion of a medicament delivery device,according to an embodiment.

FIG. 43 is a cross-sectional side view of a portion of the medicamentdelivery device shown in FIG. 42, taken along line X-X.

FIG. 43 is a top view of a portion of a medicament delivery device,according to an embodiment.

FIG. 44 is a perspective view of a portion of a medicament deliverydevice, according to an embodiment.

FIGS. 45 and 46 are a perspective view and a top view, respectively, ofa portion of a medicament delivery device, according to an embodiment.

FIG. 47 is a top view of a portion of a medicament delivery device,according to an embodiment.

FIGS. 48-50 are schematic illustrations of a disaggregation chamber of amedicament delivery device, according to an embodiment.

FIG. 51 is a schematic illustration of a disaggregation chamber of amedicament delivery device, according to an embodiment.

FIGS. 52 and 53 are top views of a medicament delivery device andpackaging system, according to an embodiment.

DETAILED DESCRIPTION

Medicament delivery devices, drug products, and methods foradministration of dry powder medicaments are described herein. In someembodiments, an apparatus includes a first member and a second membercoupled to the first member. The first member defines at least a portionof a disaggregation chamber containing a dry powder and includes achamber wall that forms an outer boundary of the disaggregation chamber.The second member includes a surface covering the disaggregation chamberand defines an intake channel and an exit channel. The exit channel isconfigured to be fluidically coupled to the disaggregation chamber viaan exit opening defined by the surface of the second member. The intakechannel is configured to be fluidically coupled to the disaggregationchamber via an intake port. A center line of a portion of the intakechannel is tangential to a portion of the chamber wall of the firstmember such that a portion of an inlet airflow conveyed into thedisaggregation chamber via the intake channel has a rotational motionabout a center axis of the disaggregation chamber. The center line canbe tangential in one plane (e.g., a top view) and non-tangential inother planes (e.g., a side view). The intake port is defined at least inpart by an intake ramp. The intake ramp includes a transition surfacethat forms an exit angle with respect to the surface of less than 105degrees.

Similarly stated, the transition surface is such that a second portionof the inlet airflow enters the disaggregation chamber at a flow angleof at least about 75 degrees (measured along the center line of theportion of the intake channel). In some embodiments, the transitionsurface is parallel to the center axis of the disaggregation chamber (oris normal to the surface of the second member). The structure of thetransition surface advantageously produces a sudden expansion into thedisaggregation chamber, which causes the second portion of the inletairflow to recirculate or “fan out” in one or more directions that arenot tangential to the chamber wall. This arrangement produces improveddisaggregation and/or clearance of the dry powder and mixing of theparticles within the airflow.

In some embodiments, the apparatus can further include a strip betweenthe first member and the second member that retains the dry powderwithin the portion of the disaggregation chamber. In this manner, thedisaggregation chamber can function both as a storage chamber and adisaggregation chamber that ensures the desired delivery characteristicsof the powder stored therein. The strip fluidically isolates the portionof the disaggregation chamber from the intake channel and the exitchannel when the strip is in a first position. The strip is configuredto be moved relative to the first member to a second position to placethe portion of the disaggregation chamber in fluid communication withthe intake channel and the exit channel.

In some embodiments, an apparatus includes a first member and a secondmember coupled to the first member. The first member defines at least aportion of a disaggregation chamber containing a dry powder and includesa chamber wall that forms an outer boundary of the disaggregationchamber. The second member includes a surface covering thedisaggregation chamber and defines an intake channel and an exitchannel. The exit channel is fluidically coupled to the disaggregationchamber via an exit opening defined by the surface of the second member.The intake channel is configured to be fluidically coupled to thedisaggregation chamber via an intake port. A center line of the intakechannel is tangential to a portion of the chamber wall of the firstmember such that a first portion of an inlet airflow conveyed into thedisaggregation chamber via the intake channel has a rotational motionabout the exit opening. The center line can be tangential in one plane(e.g., a top view) and non-tangential in other planes (e.g., a sideview). The intake port defined at least in part by an intake ramp thatis ramp curved outwardly towards the chamber wall such that a secondportion of the inlet airflow conveyed into the disaggregation via theintake channel is conveyed towards the chamber wall.

In some embodiments, the first member and the second member can bemonolithically constructed.

In some embodiments, the intake ramp defines a first radius of curvaturewithin a first plane normal to a center axis and a second radius ofcurvature within a second plane normal to the first plane. The firstradius of curvature and the second radius of curvature each openoutwardly towards the chamber wall. This arrangement causes a portion ofthe flow entering the disaggregation chamber (i.e., the second portion)to cross the path of the rotational flow within the disaggregationchamber (i.e., the first portion). This produces disruption of therotational flow and dispersion of particles circulating in therotational flow stream toward the outlet hole. Thus, this arrangementproduces reduced dose release time and higher emitted dose percentage.

In some embodiments, an apparatus includes a first member and a secondmember coupled to the first member. The first member defines at least aportion of a disaggregation chamber containing a dry powder and includesa chamber wall that forms a boundary of the disaggregation chamber. Thesecond member includes an inner surface and an outer surface and definesan intake channel and an exit channel The inner surface covers thedisaggregation chamber. The exit channel is fluidically coupled to thedisaggregation chamber via an exit opening defined by the inner surfaceof the second member. The intake channel is fluidically coupled to thedisaggregation chamber via an intake port. The intake channelfluidically coupled to an external volume outside of the disaggregationchamber by an external opening defined by the outer surface. The outersurface includes one or more barrier surfaces at least partiallysurrounding the external opening and that are configured to limitobstruction of the external opening.

In some embodiments, the barrier surfaces are formed from a set ofprotrusions extending from the outer surface of the second member. Insome embodiments, the barrier surfaces are non-planar surface (orcollectively form a set of non-planar surfaces). This arrangement canreduce the likelihood that a user's finger or other object will obstructthe external opening.

In some embodiments, an apparatus includes a lower member and an uppermember coupled to the lower member. The lower member defines at least alower portion of a disaggregation chamber containing a dry powder. Thelower member includes a raised surface along a center axis of thedisaggregation chamber. The upper member includes a surface thatencloses the disaggregation chamber and defines an upper portion of thedisaggregation chamber, the upper member defines an intake channel andan exit channel. The intake channel is fluidically coupled to thedisaggregation chamber via an intake opening, and the exit channel isfluidically coupled to the disaggregation chamber via an exit openingdefined by the surface of the upper member. The exit opening is alongthe center axis. The upper member includes a protrusion extending fromthe surface, the protrusion in contact with the raised surface tomaintain a distance between the raised surface and the exit opening.

In some embodiments, an apparatus includes an upper portion and a lowerportion that collectively define a disaggregation chamber. At least oneof the upper or lower portion can include flow structures, such asvanes, ramps, or protrusions that produce a flow pattern to repeatablydisaggregate a dry powder by controlling powder release timing and swirltime duration of the dry powder stored within the disaggregationchamber.

In some embodiments, an apparatus includes a lower member and an uppermember coupled to the lower member. The lower member defines at least alower portion of a disaggregation chamber containing a dry powder. Thelower member includes a raised surface along a center axis of thedisaggregation chamber. The upper member includes a surface thatencloses the disaggregation chamber and defines an upper portion of thedisaggregation chamber, the upper member defines an intake channel andan exit channel. The intake channel is fluidically coupled to thedisaggregation chamber via an intake opening, and the exit channel isfluidically coupled to the disaggregation chamber via an exit openingdefined by the surface of the upper member. The lower member and theupper member are collectively configured to deliver a dose of the drypowder independent of an orientation of the lower member and the uppermember. For example, in some embodiments, the exit opening is oppositefrom the raised surface, thus the dose of dry powder is delivered via anannular opening between the raised surface of the lower member and thesurface of the upper member. The annular opening (or gap) can preventpowder from remaining on the surface of the upper member if theapparatus is turned upside down. The intake channel also limits thelikelihood that the powder will exit (or be spilled) backwards out ofthe dose chamber by including a series of bends (or a tortuous path).

In some embodiments, a method includes delivering a dose of dry powderfrom a unit-dose dry powder drug product during patient inspiration. Themethod includes removing a safety tab and placing an exit opening withina mouth. An airflow is then produced by inspiration, the inspirationoccurring for an inspiration time period during which between about 2liters and 4 liters of air are drawn through the device. In someembodiments, the inspiration time period is at least about four seconds.In response to the airflow, the dry powder is disaggregated within achamber and delivered via the exit opening. In some embodiments, the drypowder is disaggregated within the chamber for a disaggregation timeperiod of at least about two seconds.

In some embodiments, a method includes moving a strip from a firstposition between a first member of a dry powder inhaler and a secondmember of the dry powder inhaler to a second position. The strip seals adry powder within a portion of a disaggregation chamber defined by achamber wall of the first member when the strip is in the firstposition. The portion of the disaggregation chamber is in fluidcommunication with an exit channel defined by the second member and anintake channel defined by the second member when the strip is in thesecond position. A mouthpiece of the dry powder inhaler is placed into amouth. The method further includes inhaling into the mouth to draw aninlet airflow through the intake channel and into the disaggregationchamber. A portion of the intake channel is tangential to a portion ofthe chamber wall of the first member such that a portion of an inletairflow has a rotational motion within the disaggregation chamber. Theportion of the intake channel can be tangential in one plane (e.g., atop view) and non-tangential in other planes (e.g., a side view). Therotational motion disaggregates the dry powder to produce a plurality ofrespirable particles within the inlet airflow. The intake channel andthe exit channel collectively configured to produce an exit airflowcontaining the plurality of respirable particles for at least twoseconds.

In some embodiments, a kit includes a package containing a dry powderinhaler and an applicator. The dry powder inhaler is configured todeliver a single dose of a dry powder medicament. The applicator isconfigured to be removably coupled to the dry powder inhaler and allowsa caregiver to position the dry powder inhaler for a user withouttouching the patient or the dry powder inhaler. In this manner, theapplicator facilitates maintaining sterility during drug delivery, aswell as protecting the caregiver (or administrator) from contamination.

Methods of assembling a medical device are described herein. In someembodiments, a method includes conveying a dry powder into a portion ofa disaggregation chamber defined by a first member of a medical device.A strip is coupled to an inner surface of the first member to seal thedry powder within the portion of the disaggregation chamber. A secondmember of the medical device is placed in contact with the first membersuch that an inner surface of the second member covers the portion ofthe disaggregation chamber. The second member defines an intake channeland an exit channel. The exit channel is configured to be fluidicallycoupled to the disaggregation chamber via an exit opening defined by theinner surface of the second member. The intake channel configured to befluidically coupled to the disaggregation chamber via an intake port. Aflange extending from the inner surface of the first member is deformedto be matingly coupled to a joint surface of the second member to form asealed joint between the first member and the second member.

In some embodiments, the flange is deformed by heat staking or heatswaging the flange to bend the flange against the joint surface. Suchmethods of assembly can limit potential adverse effects on the powderthat may results from high temperatures or other methods of joining(e.g., ultrasonic welding, radio frequency welding, or the like). Suchmethods are also easy to implement, thereby reducing the cost andcomplexity of producing the medical device. Heat-swaging the flange canproduce a more air-tight (or hermetic) seal than certain other joiningmethods, such as press fits, etc.

In some embodiments, the first member and the second member aremonolithically constructed from a degradable material, such as, forexample, a degradable material that is biodegradable, degradable viaexposure to ultraviolet radiation, or degradable, fragmentable,compostable via exposure to any combination of ultraviolet lightradiation, oxygen, moisture and biological organisms.

In some embodiments, any of the devices, dry powder inhalers, or methodscan contain a dry powder that includes a bronchodilator, such as any ofalbuterol sulfate, levalbuterol, ipratropium, albuterol/ipratropium,pirbuterol, or fenoterol.

As used herein, the words “proximal” and “distal” refer to directioncloser to and away from, respectively, a location of administration to apatient. Thus, for example, the end of the medicament delivery devicecontacting the patient's body for delivery (e.g., the mouth) would bethe distal end of the medicament delivery device, while the end oppositethe distal end would be the proximal end of the medicament deliverydevice. It is contemplated that any of the devices described herein canbe administered or actuated by either the patient themselves (i.e.,self-administration) or a caregiver (e.g., an operator, medicalprofessional, or other administrator).

As used herein, spatially relative terms—such as “beneath”, “below”,“lower”, “above”, “upper”, “proximal”, “distal”, and the like—may beused to describe the relationship of one element or feature to anotherelement or feature as illustrated in the figures. These spatiallyrelative terms are intended to encompass different positions (i.e.,translational placements) and orientations (i.e., rotational placements)of a device in use or operation in addition to the position andorientation shown in the figures. For example, if a device in thefigures is turned over, elements described as “below” or “beneath” otherelements or features would then be “above” or “over” the other elementsor features. Thus, the term “below” can encompass both positions andorientations of above and below. A device may be otherwise oriented(e.g., rotated 90 degrees or at other orientations) and the spatiallyrelative descriptors used herein interpreted accordingly.

The term “about” when used in connection with a referenced numericindication means the referenced numeric indication plus or minus up to10 percent of that referenced numeric indication. For example, “about100” means from 90 to 110.

The term “substantially” when used in connection with, for example, ageometric relationship, a numerical value, and/or a range is intended toconvey that the geometric relationship (or the structures describedthereby), the number, and/or the range so defined is nominally therecited geometric relationship, number, and/or range. For example, twostructures described herein as being “substantially parallel” isintended to convey that, although a parallel geometric relationship isdesirable, some non-parallelism can occur in a “substantially parallel”arrangement. By way of another example, a structure defining a mass thatis “substantially 90 micrograms (mcg)” is intended to convey that, whilethe recited volume is desirable, some tolerances can occur when thevolume is “substantially” the recited mass (e.g., 90 mcg). Suchtolerances can result from manufacturing tolerances, measurementtolerances, and/or other practical considerations (such as, for example,minute imperfections, age of a structure so defined, a pressure or aforce exerted within a system, and/or the like). As described above, asuitable tolerance can be, for example, of ±10% of the stated geometricconstruction, numerical value, and/or range. Furthermore, although anumerical value modified by the term “substantially” can allow forand/or otherwise encompass a tolerance of the stated numerical value, itis not intended to exclude the exact numerical value stated.

As used herein, the term “set” can refer to multiple features or asingular feature with multiple parts. For example, when referring to setof walls, the set of walls can be considered as one wall with multipleportions, or the set of walls can be considered as multiple, distinctwalls. Thus, a monolithically-constructed item can include a set ofwalls. Such a set of walls can include, for example, multiple portionsthat are either continuous or discontinuous from each other. A set ofwalls can also be fabricated from multiple items that are producedseparately and are later joined together (e.g., via a weld, an adhesive,or any suitable method).

The term “fluid-tight” is understood to encompass hermetic sealing(i.e., a seal that is gas-impervious) as well as a seal that is onlyliquid-impervious. The term “substantially” when used in connection with“fluid-tight,” “gas-impervious,” and/or “liquid-impervious” is intendedto convey that, while total fluid imperviousness is desirable, someminimal leakage due to manufacturing tolerances, or other practicalconsiderations (such as, for example, the pressure applied to the sealand/or within the fluid), can occur even in a “substantiallyfluid-tight” seal. Thus, a “substantially fluid-tight” seal includes aseal that prevents the passage of a fluid (including gases, liquidsand/or slurries) therethrough when the seal is maintained at pressuresof less than about 10 kPa. Any residual fluid layer that may be presenton a portion of a wall of a container after component defining a“substantially-fluid tight” seal are moved past the portion of the wallare not considered as leakage.

In some embodiments, a drug product configured for administration by anuntrained or partially-trained user (such as self-administration by auser) can include any of the medicament compositions described herein.Such drug products can include, for example, a dry powder deliverydevice configured to provide repeatable (e.g., device-to-device) andaccurate dose delivery. One example of such a medicament delivery deviceis provided in FIGS. 1-3, which are schematic illustrations of amedicament delivery device (or drug product) 600 according to anembodiment. The medicament delivery device 600 includes a first member(or portion) 620 and a second member (or portion) 650 coupled to thefirst member 620. The first member 620 defines at least a portion of adisaggregation chamber 625 (also referred to as a dose chamber) thatcontains a dry powder P. More particularly, the first member 620includes a chamber wall 630 (shown as a dashed line in FIGS. 1 and 2)that forms an outer boundary of the disaggregation chamber 625. Thechamber wall 630 is curved and defines a center axis CA. As describedbelow, in use, a portion of an inlet air flow can flow in a rotational(or swirling manner) within the chamber 625, bounded by the chamber wall630, as shown by the arrow A1. The chamber 625 can be configured suchthat, as the dry powder P is disaggregated into particles (shown in FIG.2) within the desired size range, the particles are entrained in theairflow and exit the chamber 625 via an exit opening 656 that is definedby the second member 650. Although the chamber wall 630 is shown asbeing circular, in other embodiments, the chamber wall 630 (and any ofthe chambers described herein) can have any suitable shape. For example,in some embodiments, the chamber wall 630 can be oval, elliptical,polygonal, or spiral shaped.

The second member 650 includes an inner surface 651 (see FIG. 3) thatcovers the disaggregation chamber 625. The inner surface 651 can becoupled to a corresponding inner surface of the first member 620 by anysuitable mechanism described herein. The slight gap shown in FIG. 3between the first member 620 and the second member 650 is only forpurposes of illustration to more clearly identify the inner surface 651.In reality, the first member 620 is coupled to the second member 650 ina manner that prevents air leakage from the interface between the firstmember 620 and the second member 650. The second member 650 defines anintake channel 660 and an exit channel 674. The exit channel 674 isconfigured to be fluidically coupled to the disaggregation chamber 625via an exit opening 656 defined by the surface 651 of the second member650. In this manner, when a user inhales on the exit channel 674, inletair can be drawn from the disaggregation chamber 625 through the exitopening 656 and into the exit passageway 674 to deliver a dose of thedry powder P to the user.

As viewed from the top (FIGS. 1 and 2), the intake channel 660 defines acenter line CL that is tangential to a portion of the chamber wall 630of the first member 620 such that a first portion of an inlet airflow(shown as arrow A3 in FIG. 3) conveyed into the disaggregation chamber625 via the intake channel 660 initiates a rotational flow A1 andparticle motion about the center axis CA of the disaggregation chamber625. Similarly stated, at least a portion of the intake channel 660 isshaped and positioned with respect to the disaggregation chamber 625such that the linear momentum of the first portion of the inlet airflowwithin the intake channel 660 is transformed into an angular momentumwithin the disaggregation chamber 625 (about the center axis CA). Inthis manner, the intake channel 660 produces a rotational (or swirling)airflow with disruption at air inlet location(s)within thedisaggregation chamber 625. In some embodiments, the center line CL canbe tangential in one plane (e.g., a top view, FIG. 1) and non-tangentialin other planes (e.g., a side view, FIG. 3). In other embodiments, thecenter line CL need not be tangential to a portion of the chamber wall630.

The intake channel 660 is configured to be fluidically coupled to thedisaggregation chamber 625 via an intake port 665. As described herein,the characteristics of the inlet air flow as it enters thedisaggregation chamber 625 can impact the accuracy and repeatabilitywith which the dry powder P is disaggregated, broken up, and/orotherwise prepared for delivery to the user. For example, in addition tothe dose chamber 625 shape and dimensions (e.g. depth and diameter), theshape and size of the inlet passageways can influence the airflowpattern within the chamber 625 (see, e.g., the arrow A1 in FIG. 2).Referring to FIG. 3, the intake port 665 is defined at least in part byan intake ramp 667 that includes a transition surface 668. Thetransition surface 668 intersects the inner surface 651 to form an edgeor interrupted edge of the second member 650. As shown in FIG. 3, thetransition surface 668 forms an exit angle ⊖ with respect to the surface651. The exit angle ⊖ can impact the dose release timing by controllingthe number of revolutions that entrained particles make within thechamber 625 before exiting, the efficiency of disaggregation, thepercentage of the dose emitted, and the like. Thus, the intake port 665and the transition surface 668 are configured to produce the desiredinlet airflow into the disaggregation chamber 625 such that the desiredexit characteristics (e.g., dose release timing, particle sizedistribution, percentage of dose emitted) are achieved. For example, insome embodiments, the drug product 600 (or any other drug productsdescribed herein) can produce a particle size distribution well suitedfor reaching the deeper areas (e.g., alveoli) of the lungs.

In some embodiments, the exit angle ⊖ is less than 105 degrees.Similarly stated, the transition surface 668 is angled such that asecond portion of the inlet airflow A2 enters the disaggregation chamberat a flow angle of at least about 75 degrees (measured along the centerline CL of the intake channel 660). In some embodiments, the transitionsurface is parallel to the center axis CA of the disaggregation chamber625 (i.e., the exit angle ⊖ is about 90 degrees). By having an exitangle ⊖ of less 105 degrees (or at about 90 degrees), the transitionsurface 668 advantageously produces a sudden expansion into thedisaggregation chamber 625 (as opposed to a more gradual diffusion intothe disaggregation chamber 625). This arrangement produces disruption ofrotational air flow A1 when a portion of intake flow A2 is conveyed fromthe intake channel 660 to the disaggregation chamber 625. In someembodiments, the intake air flow generated by the intake channel 660 andtransition to the disaggregation chamber 625 can produce a rotationalflow component A3 in FIG. 3 as well as a disruptive flow component asindicated by A2 in FIG. 3, or can otherwise cause the second portion A2of the inlet airflow to disrupt rotational flow A1 (shown in FIG. 2) and“fan out” the rotational air-particle stream in one or more directionsthat are not tangential to the chamber wall 630. This non-tangentialflow direction is shown by the arrows A2 in FIG. 2, and is similar tothe flow structure and concepts described within reference to the device100 shown in FIG. 29. This arrangement of disrupted rotational flowenables particles to more easily flow to the exit opening 656 of thedisaggregation chamber 625, reduces dose release timing, and provides ahigher emitted dose percentage. In some embodiments, the edge betweenthe transition surface 668 and the inner surface 651 can be asubstantially sharp edge (e.g., have an edge radius of less than about130 microns (0.005 inches)). This can further enhance flow separation or“fan out” of the second portion of the inlet airflow A2 as air isconveyed through the intake port 665 and into the disaggregationchamber. In other embodiments, however, the edge between the transitionsurface 668 and the inner surface 651 can be curved or have a radius ofgreater than about 130 microns (i.e., can include an edge break).

The dry powder P included in the medicament delivery device 600 (or anyof the devices described herein) can include any suitable medicament,nutraceutical, or composition. In some embodiments, any of themedicament delivery devices (or drug products) described herein caninclude a composition including any suitable active pharmaceuticalingredient (API), any suitable excipient, bulking agent, carrierparticle, or the like.

In some embodiments, the API can include albuterol sulfate (alsoreferred to as “sulphate,” for example, in Europe). In otherembodiments, any of the drug products described herein can include anyother bronchodilator. For example, in some embodiments the API caninclude a short-acting bronchodilator, such as, for example,levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, and/orfenoterol. For example, in some embodiments the API can include along-acting bronchodilator, such as, for example, aclidinium (Tudorza),arformoterol (Brovana), formoterol (Foradil, Perforomist),glycopyrrolate (SeebriNeohaler), indacaterol (Arcapta), olodaterol(Striverdi Respimat), salmeterol (Serevent), tiotropium bromide(Spiriva), umeclidinium (IncruseEllipta), mometasone furoate powder,flunisolide, budesonide, and/or vilanterol.

As described herein, the dry powder P can also include any suitableexcipient, such as, for example, lactose. The dry powder P can ofteninclude predominantly the excipient with a small percentage of the massbeing the API (e.g., one to ten percent). Thus, the deliverycharacteristics of the device 600 can be highly dependent on the lactosecharacteristics (or the grade of lactose included within the dry powderP). For example, some dry powder P can include a non-sieved lactose witha mean diameter of 60 microns. Such powder formulations thereforeinclude the fine lactose particles (e.g., 1-5 microns), and thus can bemore “sticky” than those formulations that do not include as much of thefine particles. The advantage of using such non-sieved lactose is that ahigher percentage of fine particles can be delivered, which can bebeneficial for the desired treatment (e.g., deep lung delivery or thelike). Such non-sieved formulations, however, can require more turbulentairflow to disaggregate the stickier fine particles than is needed for asieved formulation. Thus, the transition surface 668 and the exit angle⊖ can be optimized for use with (and can provide the desired amount ofdisruptive airflow) for a non-sieved formulation. Thus, in someembodiments, the dry powder P can include a non-sieved lactoseformulation having a mean particle diameter of 60 microns. In otherembodiments, the dry powder P can include a sieved lactose formulationhaving an initial mean particle diameter of 60 microns, but with asubstantial amount of the fine particles removed by the sieve operation.

In some embodiments, the medicament delivery device 600 can include astrip or seal (not shown) that fluidically isolates the portion of thedisaggregation chamber 625 from the intake channel 660 and/or the exitchannel 674. In this manner, the disaggregation chamber 625 functions asa chamber (or a portion of a chamber) within which the dry powder can beboth stored and later disaggregated. The strip (or seal) can be anysuitable seal shown and described herein (e.g., the strip 110 of thedevice 100 shown below), or can be similar to the partition 95 shown anddescribed in U.S. Pat. No. 9,446,209 (filed Mar. 7, 2014), entitled “DryPowder Inhalation Device,” which is incorporated herein by reference inits entirety. For example, in some embodiments, a strip can be coupledbetween the first member 620 and the second member 650 (e.g., in contactwith the inner surface 651) to seal and/or maintain the dry powder Pwithin the chamber 625. Any such seal member can be formulated to becompatible with any of the medicaments and/or drug compositions disposedwithin the chamber 625. Similarly stated, the seal member can beformulated to minimize any reduction in the efficacy of the drugcompositions that may result from contact (either direct or indirect)between the seal member and the drug composition within the chamber 625.For example, in some embodiments, the seal member can be formulated tominimize any leaching or out-gassing of compositions that may have anundesired effect on the drug composition within the device 600. In otherembodiments, the seal member can be formulated to maintain its chemicalstability, flexibility, strength, and/or sealing properties when incontact (either direct or indirect) with the drug composition within thedevice 600 over a long period of time (e.g., for up to six months, oneyear, two years, five years, or longer).

In use, the user first removes any packaging or overwrap (not shown inFIGS. 1-3, see the overwrap 711 described below) from about the device600. The user can then optionally remove any seal from between the firstmember 620 and the second member 650. The user then places a portion ofthe device (e.g., a mouthpiece) into or against their mouth. The userthen inhales, which draws air through the intake channel 660 and intothe disaggregation chamber 625. As described above, the inlet airflow isdrawn through the inlet port 665, which imparts the desired flowcharacteristics to the inlet airflow as it enters the chamber 625. Theinlet airflow moves within the chamber 625 (see, e.g., the arrows A1 andA2 in FIG. 2) and entrains the dry powder P stored therein. Continueddynamic motion of the inlet airflow causes disaggregation of theparticles, thus producing the desired drug delivery performancecharacteristics (e.g., emitted dose, fine particle mass) for delivery tothe patient via the exit channel 674.

The medicament delivery device 600 (and any of the medicament deliverydevices described herein) can be constructed from any suitable materialsand can be assembled according to any of the methods described herein.For example, in some embodiments, the first member 620 and the secondmember 650 are monolithically constructed from a polymeric material. Insome embodiments, the material can be a degradable material, such as,for example, a degradable material that is biodegradable, degradable viaexposure to ultraviolet radiation, or degradable, fragmentable,compostable via exposure to any combination of ultraviolet lightradiation, oxygen, moisture and biological organisms.

Although the intake ramp 667 of the intake port 665 described above isshown as having a curved surface in one plane, in other embodiments, amedicament delivery device can include an intake port having anysuitable curved structure to facilitate production of the desired flow.Similarly stated, although the intake ramp 667 is shown as beingrectangular shaped when viewed in a first plane normal to the centeraxis CA (e.g., the top view of FIGS. 1 and 2) and curved in a secondplane parallel to the center axis CA (e.g., the side view of FIG. 3), inother embodiments, an intake port can include curved surfaces in anyplane (or planes). For example, FIGS. 4-7 are schematic illustrations ofa medicament delivery device (or drug product) 700 according to anembodiment. The medicament delivery device 700 includes a first member(or portion) 720 and a second member (or portion) 750 coupled to thefirst member 720. The first member 720 defines at least a portion of adisaggregation chamber 725 that contains a dry powder P. Moreparticularly, the first member 720 includes a chamber wall 730 (shown asa dashed line in FIGS. 4, 5, and 7) that forms an outer boundary of thedisaggregation chamber 725. The chamber wall 730 is curved and defines acenter axis CA. As described below, in use, a portion of an inlet airflow can flow in a rotational (or swirling manner) within the chamber725, bounded by the chamber wall 730, as shown by the arrow A1. Thechamber 725 can be configured such that, as the dry powder P isdisaggregated into particles (identified as particles P1 and P2 in FIGS.5 and 7) within the desired size range, the particles are entrained inthe airflow and exit the chamber 725 via an exit opening 756 that isdefined by the second member 750. Although the chamber wall 730 is shownas being circular, in other embodiments, the chamber wall 730 (and anyof the chambers described herein) can have any suitable shape. Forexample, in some embodiments, the chamber wall 730 can be oval,elliptical, polygonal, or spiral shaped.

The second member 750 includes an inner surface 751 (see FIG. 6) thatcovers the disaggregation chamber 725. The inner surface 751 can becoupled to a corresponding inner surface of the first member 720 by anysuitable mechanism described herein. The slight gap shown in FIG. 3between the first member 720 and the second member 750 is only forpurposes of illustration to more clearly identify the inner surface 751.In reality, the first member 720 is coupled to the second member 750 ina manner that prevents air leakage from the interface between the firstmember 720 and the second member 750. The second member 750 defines anintake channel 760 and an exit channel 774. The exit channel 774 isconfigured to be fluidically coupled to the disaggregation chamber 725via an exit opening 756 defined by the surface 751 of the second member750. In this manner, when a user inhales on the exit channel 774, inletair can be drawn from the disaggregation chamber 725 through the exitopening 756 and into the exit passageway 774 to deliver a dose of thedry powder P, and specifically the fine particles P2, to the user.

The intake channel 760 defines a center line CL that is tangential to aportion of the chamber wall 730 of the first member 720 such that afirst portion of an inlet airflow (shown as arrow A1 in FIGS. 5 and 7)conveyed into the disaggregation chamber 725 via the intake channel 760has a rotational motion about the center axis CA of the disaggregationchamber 725 and/or the exit opening 756. Similarly stated, at least aportion of the intake channel 760 is shaped and positioned with respectto the disaggregation chamber 725 such that the linear momentum of thefirst portion of the inlet airflow within the intake channel 760 istransformed into an angular momentum within the disaggregation chamber725 (about the center axis CA). In this manner, the intake channel 760produces a rotational (or swirling) airflow within the disaggregationchamber 725. In some embodiments, the center line CL can be tangentialin one plane (e.g., a top view, FIG. 4) and non-tangential in otherplanes (e.g., a side view, FIG. 6). In other embodiments, the centerline CL need not be tangential to a portion of the chamber wall 730.

The intake channel 760 is configured to be fluidically coupled to thedisaggregation chamber 725 via an intake port 765. As described herein,the characteristics of the inlet air flow as it enters thedisaggregation chamber 725 can impact the accuracy and repeatabilitywith which the dry powder P is disaggregated, broken up, and/orotherwise prepared for delivery to the user. Referring to FIG. 6, theintake port 765 is defined at least in part by an intake ramp 767 thatis curved outwardly towards the chamber wall 730. This arrangementcauses a second portion A2 of the inlet airflow to be conveyed outwardlytowards the chamber wall 730 when conveyed from the intake channel 760to the chamber 725. In this manner, the rotational flow within thedisaggregation chamber 725 is biased towards and deflects off theoutside portion of the disaggregation chamber 725, toward the exitopening 756. Similarly stated, the second portion of the airflow A2 can“bounce” off the outer portion of the wall 730 and be conveyed throughthe first portion of the airflow A1 and toward the exit opening 756.Thus, the particles circulating within the first portion A1 of the inletairflow will flow through (and be disrupted by) the second portion A2 ofthe inlet airflow. Similarly stated, the different direction of airflowstreams produces reduced dose release time and increased emitted dosepercentage.

Additionally, by deflecting and biasing the rotational flow within thedisaggregation chamber 725 toward the exit opening 756, the length oftime during which a series of particles resides within thedisaggregation chamber 725 is reduced. Similarly stated, deflecting andbiasing the rotational flow within the disaggregation chamber 725 towardthe exit opening 756 causes the effective clearance of large and/orcohesive powder doses from the disaggregation chamber 725.

Referring to FIGS. 4 and 6, in some embodiments, the intake ramp 767 canbe curved outwardly towards the chamber wall 730 in multiple planes. Forexample, the intake ramp 767 defines a first radius of curvature R1within a first plane normal to the center axis CA (e.g., the top view ofFIG. 4). The intake ramp 767 also defines a second radius of curvatureR2 within a second plane parallel to the center axis CA (e.g., the sideview of FIG. 6).

In some embodiments, the medicament delivery device 700 can includeproperties or characteristics of the medicament delivery device 600, andvice-versa. For example, in some embodiments, the intake ramp 767 caninclude a transition surface similar to the transition surface 668 shownand described above. For example, in some embodiments, the intake ramp767 can include a transition surface that forms an exit angle of lessthan about 105 degrees. In some embodiments, the intake ramp 767 caninclude a transition surface that forms a substantially sharp edge(e.g., have an edge radius of less than about 130 microns) with theinner surface 751.

The dry powder P included in the medicament delivery device 700 (or anyof the devices described herein) can include any suitable medicament,nutraceutical, or composition. In some embodiments, any of themedicament delivery devices (or drug products) described herein caninclude a composition including any suitable active pharmaceuticalingredient (API), any suitable excipient, bulking agent, carrierparticle, or the like.

In some embodiments, the API can include albuterol sulfate. In otherembodiments, any of the drug products described herein can include anyother bronchodilator. For example, in some embodiments the API caninclude a short-acting bronchodilator, such as, for example,levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, and/orfenoterol. For example, in some embodiments the API can include along-acting bronchodilator, such as, for example, aclidinium (Tudorza),arformoterol (Brovana), formoterol (Foradil, Perforomist),glycopyrrolate (SeebriNeohaler), indacaterol (Arcapta), olodaterol(Striverdi Respimat), salmeterol (Serevent), tiotropium bromide(Spiriva), umeclidinium (IncruseEllipta), mometasone furoate powder,flunisolide, budesonide, and/or vilanterol.

As described herein, the dry powder P can also include any suitableexcipient, such as, for example, lactose. The dry powder P can ofteninclude predominantly the excipient with a small percentage of the massbeing the API (e.g., one to ten percent). Thus, the deliverycharacteristics of the device 700 can be dependent on the lactosecharacteristics (or the grade of lactose included within the dry powderP). For example, some dry powder P can include a non-sieved lactose witha mean diameter of 60 microns. Such powder formulations thereforeinclude the fine lactose particles (e.g., 1-5 microns), and thus can bemore “sticky” than those formulations that do not include as much of thefine particles. The advantage of using such non-sieved lactose is that ahigher percentage of fine particles can be delivered, which can bebeneficial for the desired treatment (e.g., deep lung delivery or thelike). Such non-sieved formulations, however, can require more turbulentairflow to disaggregate the stickier fine particles than is needed for asieved formulation. Thus, the ramp 667 can be optimized for use with(and can provide the desired amount of disruptive airflow) for anon-sieved formulation. Thus, in some embodiments, the dry powder P caninclude a non-sieved lactose formulation having a mean particle diameterof 60 microns. In other embodiments, the dry powder P can include asieved lactose formulation having an initial mean particle diameter of60 microns, but with a substantial amount of the fine particles removedby the sieve operation.

In some embodiments, the medicament delivery device 700 can include astrip or seal (not shown) that fluidically isolates the portion of thedisaggregation chamber 725 from the intake channel 760 and/or the exitchannel 774. In this manner, the disaggregation chamber 725 functions asa chamber (or a portion of a chamber) within which the dry powder can beboth stored and later disaggregated. The strip (or seal) can be anysuitable seal shown and described herein (e.g., the strip 110 shownbelow), or can be similar to the partition 95 shown and described inU.S. Pat. No. 9,446,209 (filed Mar. 7, 2014), entitled “Dry PowderInhalation Device,” which is incorporated herein by reference in itsentirety.

The medicament delivery device 700 can be used in a manner similar tothat described above for the medicament delivery device 600, or anyother methods described herein.

In some embodiments, any medicament delivery devices described hereincan include features to facilitate administration of a dry powdermedicament by an untrained or partially-trained user (such asself-administration by a user). For example, in some embodiments, amedicament delivery device can include features to limit variation inthe airflow resistance through the device. In this manner, the accuracyand repeatability of the device, including the flow rates, velocities,amount of the delivered and/or fine particle fraction of the delivereddose can be improved. For example, in some embodiments, a medicamentdelivery device can include spacers, protrusions, or the like configuredto limit inadvertent or undesired deformation in flow channels (e.g.,deformation or blocking of flow paths due to the patient gripping thedevice). In other embodiments, a medicament delivery device can includeone or more barrier surfaces that limit the likelihood that an externalopening through which air is drawn will become blocked. For example,FIG. 8 is a schematic illustration of a medicament delivery device (ordrug product) 900 according to an embodiment. The medicament deliverydevice 900 includes a first member (or portion) 920 and a second member(or portion) 950 coupled to the first member 920. The first member 920defines at least a portion of a disaggregation chamber 925 that containsa dry powder (not shown). More particularly, the first member 920includes a chamber wall 930 that forms a boundary of the disaggregationchamber 925. The chamber 925 can be configured such that, as the drypowder is disaggregated into particles within the desired size range,the particles are entrained in the airflow and exit the chamber 925 viaan exit opening 956 that is defined by the second member 950 (see theexit airflow Aout in FIG. 8). Although the chamber wall 930 is shown asbeing curved, in other embodiments, the chamber wall 930 (and any of thechambers described herein) can have any suitable shape. For example, insome embodiments, the chamber wall 930 can be conical, oval, elliptical,polygonal, or spiral shaped.

The second member 950 includes an inner surface 951 and an outer surface952. The inner surface 951 covers the disaggregation chamber 925 and canbe coupled to a corresponding inner surface of the first member 920 byany suitable mechanism described herein. The slight gap shown in FIG. 8between the first member 920 and the second member 950 is only forpurposes of illustration to more clearly identify the inner surface 951.In reality, the first member 920 is coupled to the second member 950 ina manner that prevents air leakage from the interface between the firstmember 920 and the second member 950. The second member 950 defines anintake channel 960 and an exit channel 974. The exit channel 974 isconfigured to be fluidically coupled to the disaggregation chamber 925via an exit opening 956 defined by the surface 951 of the second member950. In this manner, when a user inhales on the exit channel 974 (e.g.,via a mouthpiece 953), inlet air can be drawn from the disaggregationchamber 925 through the exit opening 956 and into the exit passageway974 to deliver a dose of the dry powder, as shown by the airflow Aout.

The intake channel 960 is configured to be fluidically coupled to thedisaggregation chamber 925 via an intake port 965. The intake channel960 is fluidically coupled to an external volume outside of thedisaggregation chamber 925 by an external opening 963 defined by theouter surface 952. As described herein, the characteristics of the inletair flow as it enters the disaggregation chamber 925 can impact theaccuracy and repeatability with which the dry powder P is disaggregated,broken up, and/or otherwise prepared for delivery to the user. Thus, anyobstruction of the external opening 963 can reduce the amount of inletairflow (shown as Ain), thereby changing the performance of themedicament delivery device 900. Accordingly, the outer surface 952includes one or more barrier surfaces 984 that at least partiallysurround the external opening 963. The set of barrier surfaces 984 isconfigured to limit obstruction of the external opening 963, which canbe caused, for example, by the user's fingers during use of the device.In some embodiments, the set of barrier surfaces 984 is formed from oneor more protrusions extending from the outer surface 952 of the secondmember 950. In some embodiments, the set of barrier surfaces 984 arenon-planar surfaces that at least partially surround the externalopening 963. In this manner, when a user's finger (or any other object)contacts the barrier surfaces 984, passageways for the inlet airflow Ainwill be maintained by the non-planar structure of the barrier surfaces984. In some embodiments, the set of barrier surfaces 984 defines one ormore tortuous paths within the outer surface 952 of the second member950 that are in fluid communication with the external opening 963. Inthis manner, as shown by the arrows entering the external opening 963,the barriers 984 provide a series of alternate paths through which theinlet air can be drawn.

In addition to facilitating a consistent airflow through thedisaggregation chamber 925, the medicament delivery device 900 alsolimits the likelihood that the powder within the disaggregation chamber925 will be inadvertently conveyed backwards through the intake channel960. Specifically, as shown, the intake channel 960 includes multiplebends that limit the likelihood that powder inside the disaggregationchannel 925 will be conveyed out of the chamber 925 via the intakechannel 960 by tipping and/or changing the orientation of the device 900during use. Similarly stated, the intake channel 960 includes a tortuouspath to limit movement of the dry powder from the disaggregation chamber925 through the intake channel 960 and the external opening 963.

In some embodiments, the medicament delivery device 900 can includeproperties or characteristics of the medicament delivery device 600 orany of the devices described herein, and vice-versa. For example, insome embodiments, the intake port 965 can be similar to the intake port665 or the intake port 765 described above. For example, in someembodiments, the intake port 965 can include a transition surfacesimilar to the transition surface 668 shown and described above.

In some embodiments, the medicament delivery device 900 can include astrip or seal (not shown) that fluidically isolates the portion of thedisaggregation chamber 925 from the intake channel 960 and/or the exitchannel 974. In this manner, the disaggregation chamber 925 functions asa chamber (or a portion of a chamber) within which the dry powder can beboth stored and later disaggregated. The strip (or seal) can be anysuitable seal shown and described herein (e.g., the strip 110 shownbelow), or can be similar to the partition 95 shown and described inU.S. Pat. No. 9,446,209 (filed Mar. 9, 2014), entitled “Dry PowderInhalation Device,” which is incorporated herein by reference in itsentirety.

In some embodiments, the first member 920 and the second member 950 aremonolithically constructed from a polymeric material. Moreover, in someembodiments, the barrier surfaces 984 are monolithically constructedwith the second member 950, which, in turn, can be monolithicallyconstructed with the first member 920. In this manner, the device 900can be a one-piece device that has features (e.g., the barrier surfaces984) that protect the external opening 963 from obstruction. In someembodiments, the device can be constructed from a degradable material,such as, for example, a degradable material that is biodegradable,degradable via exposure to ultraviolet radiation, or degradable,fragmentable, compostable via exposure to any combination of ultravioletlight radiation, oxygen, moisture and biological organisms.

The medicament delivery device 900 can be used in a manner similar tothat described above for the medicament delivery device 600, or anyother methods described herein.

FIGS. 9-29 show various views of a medicament delivery device (or drugproduct) 100 according to an embodiment. The medicament delivery device100 includes a lower member (or portion) 120 and an upper member (orportion) 150. FIGS. 9-17 show the lower member 120 and the upper member150 in a substantially planar configuration to clearly show the featuresof each member. FIGS. 18-20 show the medicament delivery device 100being moved from an opened (or planar) configuration to a closedconfiguration. FIGS. 21-29 show the medicament delivery device 100 withthe inner surface 151 of the upper member 150 coupled to thecorresponding inner surface 121 of the lower member 120 to form theassembled medicament delivery device 100. As shown in FIGS. 19 and 20,the upper member 150 can be rotated or “folded” onto the lower member120, as shown by the arrow AA in FIG. 13 and BB in FIG. 20, to form theassembled medicament delivery device 100. When assembled, the medicamentdelivery device 100 can be similar to, and can include certain featuresof, any of the medicament delivery devices shown and described in U.S.Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which isincorporated herein by reference in its entirety.

The lower member 120 includes a first (or inner) surface 121 (see FIGS.13 and 28) and a second (or outer) surface 122 (see FIGS. 9 and 10). Theinner surface 121 defines a chamber 125 and one or more injectionmolding gate recesses 149. The chamber 125 defines a volume or recesswithin which any suitable medicament is stored. As shown in FIG. 19, astrip 110 (also referred to as a seal member or partition) is coupled tothe inner surface 121 to seal and/or maintain a medicament within thechamber 125. The strip 110 can be any suitable member that can beremovably coupled about the chamber 125. For example, in someembodiments, the strip 110 can have a peelable heat seal coating toallow the strip 110 to be removed from the inner surface 121 by beingpeeled from the device 100. The strip 110 can be formulated to becompatible with any of the medicaments and/or drug compositions disposedwithin the chamber 125. Similarly stated, the strip 110 can beformulated to minimize any reduction in the efficacy of the drugcompositions that may result from contact (either direct or indirect)between the seal member and the drug composition within the chamber 125.For example, in some embodiments, the strip 110 can be formulated tominimize any leaching or out-gassing of compositions that may have anundesired effect on the drug composition within the device 100. In otherembodiments, the strip 110 can be formulated to maintain its chemicalstability, flexibility, strength, and/or sealing properties when incontact (either direct or indirect) with the drug composition within thedevice 100 over a long period of time (e.g., for up to six months, oneyear, two years, five years, or longer). In some embodiments, the strip110 can include a pull tab portion at the distal end. The pull tabportion can be a portion of the strip 110 that extends beyond themouthpiece of the device 100 and provides a region that the user caneasily grasp or pull to remove the strip 110.

In addition to providing a volume or reservoir within which a medicamentcan be stored, the chamber 125 also functions as a chamber (or a portionof a chamber) within which the medicament can be disaggregated orotherwise prepared for delivery to a patient. Specifically, referring toFIG. 13, the inner surface 121 includes a raised central surface 126 anddefines a central axis (or centerline) CL. Thus, when the upper member150 is coupled to the lower member 120, the chamber 155 (defined by theupper member 150) and the chamber 125 (defined by the lower member 120)define a circular shaped chamber about the raised central surface 126and the centerline CL. Thus, the chamber 125 forms at least a portion ofa disaggregation (and/or dose preparatory) chamber for the device 100.Referring to FIG. 28, the inner surface 121 includes an outer portion(or wall) 130 and an inner portion (or wall) 134, that each form aportion of (or define) the chamber 125. As described below, in use aninlet air flow can flow in a rotational (or swirling manner) within thechamber 125, bounded by the outer wall 130 and the inner wall 134, asshown by the arrow BB in FIG. 28 or the arrows A1 in FIG. 29. Thechamber 125 can be configured such that, as the medicament isdisaggregated into particles within the desired size range, theparticles are entrained in the airflow and exit the chamber 125 via anexit opening 156 that is spaced apart from (and above) the raisedsurface 126. The exit flow is shown by the arrow CC in FIG. 28 and thearrow A3 in FIG. 29.

As shown in FIGS. 12, 19, and 24, the inner surface 121 defines a recess136 that forms a gap with the mating inner surface 151 of the uppermember 150. The recess 136 provides a space within which a portion ofthe strip 110 can be bunched or deformed when being removed from betweenthe upper member 150 and the lower member 120. As described below, therecess 136 along with the walls 137 limit binding of the strip 110 orportions of the strip 110 (e.g., a pull tab) during removal.

The inner surface 121 also includes two connection flanges 144. Duringassembly, the connection flanges 144 are deformed to be matingly coupledto a joint surface 186 of the upper member 150 to form a sealed jointbetween the lower member 120 and the upper member 150.

The second (or outer surface) 122 includes two side edges 140, each ofwhich includes a series of ridges or ribs. The side edges 140 facilitategripping and manipulation of the device 100 when in its assembled state.As shown the device 100 includes a hinge portion 138 between the lowermember 120 and the upper member 150, and about which the upper member150 can be rotated about the lower member 120 (or vice versa) to formthe assembled drug product 100 (see FIG. 20). The lower member 120defines two coupling slots 142 that receive the coupling protrusions 182of the upper member 150 when the drug product 100 is in its assembledconfiguration. More particularly, the coupling protrusions 182 areconfigured to be matingly coupled within the coupling slots 142 to limitmovement of the lower member 120 relative to the upper member 150 afterthe device 100 is in its assembled configuration. In particular, in someembodiments, the device 100 can be placed in an initial closedconfiguration after being molded. The coupling protrusions 182 areconfigured to be temporarily locked within the coupling slots 142 toprevent the device 100 from being opened, unfolded, or otherwisetampered during shipment to a fill/finish operation. By being shipped inan initial (but not permanent) closed configuration, the internalgeometry (e.g., the chambers 125, 155, the inlet passageways, the exitpassageways) are protected from debris, contamination, and the like.Shipping in the closed configuration also reduces the need foradditional shipping containers or packaging, thus reducing manufacturingcosts. Although the lower member 120 is shown as defining slots 142within which the protrusions 182 are received, in other embodiments,either of the lower member 120 or the upper member 150 can define anycombination of slots, openings and/or protrusions.

The upper member 150 includes a first (or inner) surface 151 (see FIGS.13, 14 and 17) and a second (or outer) surface 152 (see FIGS. 9 and 10).The upper member 150 includes an inlet portion 153 and an exit portion170. Further, the inner surface 151 defines a chamber 155 that, alongwith the chamber 125, forms a disaggregation chamber or volume, asdescribed above. The inner surface 151 defines one or more couplingrecesses 179 for injection molding gate locations 186, and includes thecoupling protrusion 182 and the strip (or pull tab) guide walls 137, asdescribed above.

The inlet portion 153 defines a series of inlet passageways (alsoreferred to as intake channels) through which inlet air flows into thedisaggregation chamber when the patient inhales through the device 100.As described herein, the characteristics of the inlet air flow as itenters the chambers 125, 155 can impact the accuracy and repeatabilitywith which the medicament within the chambers 125, 155 is disaggregated,broken up, and/or otherwise prepared for delivery to the patient. Forexample, the shape and size of the inlet passageways can influence theairflow pattern within the chamber 125 (see, e.g., the arrow BB in FIG.28 and the arrow A1 in FIG. 29). The angle of entry, in turn, can impactthe number of revolutions that entrained particles make within thechamber 125 before exiting (see, e.g., the arrow CC in FIG. 28 and thearrow A3 in FIG. 29). Thus, the inlet portion 153 is configured toproduce the desired inlet airflow such that the desired exitcharacteristics (e.g., velocity, flow rate, particle size distribution)are achieved. For example, in some embodiments, the drug product 100 (orany other drug products described herein) can produce a particle sizedistribution well suited for reaching the deeper areas (e.g., alveoli)of the lungs.

In particular, the inlet portion 153 includes four inlet passageways(also referred to as intake channels): a first inlet passageway 160A, asecond inlet passageway 160B, a third inlet passageway 160C, and afourth inlet passageway 160D. Referring to FIG. 14, the first inletpassageway 160A includes an external opening 163A through which inletair is drawn from outside of the device 100, and intake port 165Athrough which the inlet air is conveyed into the chambers 155, 125, anda curved portion therebetween. The second inlet passageway 160B includesan external opening 163B through which inlet air is drawn from outsideof the device 100, and intake port 165B through which the inlet air isconveyed into the chambers 155, 125, and a curved portion therebetween.The third inlet passageway 160C includes an external opening 163Cthrough which inlet air is drawn from outside of the device 100, andintake port 165C through which the inlet air is conveyed into thechambers 155, 125, and a curved portion therebetween. The fourth inletpassageway 160D includes an external opening 163D through which inletair is drawn from outside of the device 100, and intake port 165Dthrough which the inlet air is conveyed into the chambers 155, 125, anda curved portion therebetween.

The outer surface 152 of the upper member 150 includes a shroud (orridge) 180 that surrounds the external openings 163A, 163B, 163C, 163D.The shroud 180 provides a surface that the user can contact whenmanipulating the device 100 when in its assembled state. As describedabove, the side edges 140 also facilitate gripping and manipulation. Theshroud 180 can be either continuous or can be interrupted about theouter edge of the upper member 150. The shroud 180 also provides abarrier adjacent the external openings that limit the likelihood thatthe external openings 163A, 163B, 163C, 163D will become obstructed bythe user's fingers or other materials during use. In addition to theshroud 180, as shown in FIGS. 21 and 22, the outer surface 152 includesa first set of barrier protrusions (or surfaces) 184 that at leastpartially surround the external opening 163A and the external opening163B. As shown in FIG. 26A, the outer surface 152 includes a second setof barrier protrusions (or surfaces) 186 that at least partiallysurround the external opening 163C and the external opening 163D. Thebarrier surfaces 184, 185 are also configured to limit obstruction ofthe external openings, which can be caused, for example, by the user'sfingers during use of the device. In particular, the set of barrierprotrusions 184 include multiple non-planar surfaces that at leastpartially surround the external openings 163A, 163B. In this manner,when a user's finger (or any other object) contacts the barrier surfaces184, passageways for the inlet airflow will be maintained by flow aroundthe non-planar structure of the barrier surfaces 184.

The intake ports 165A, 165B, 165C, 165D are located on the inner surface151 such that they open in to (or are in fluid communication with) thechamber 125 after the removal of strip (or seal) 110 that is disposedabout the chamber 125. In this manner, upon inspiration (inhalation) bythe patient, air is drawn from outside of the device through theexternal openings 163A, 163B, 163C, 163D, within the various curvedportions of each of the inlet passageways, and into the chamber 125 viathe intake ports 165A, 165B, 165C, 165D. As described above, the inletpassageways 160A, 160B, 160C, 160D can include any suitable geometry orsize to produce the desired airflow characteristics within the chamber125. For example, as shown in FIG. 17, the intake port 165A can bedefined and/or bounded by an intake ramp 167A that includes atermination edge (or surface) 168A. Similarly, FIGS. 17 and 27 shows aside cross-sectional view of a portion of the intake port 165B, which isbounded by an intake ramp 167B that includes a termination edge (orsurface) 168B. The transition of the ramps at the termination edgeintersect (or forms an edge with) the inner surface 151 of the secondmember 150. As described above with reference to the device 600, thetransition edges (or surfaces) 168A, 168B each forms an exit angle withrespect to the surface 151 that can have any suitable value. Forexample, the exit angle can be less than 105 degrees. In someembodiments, the transition surface 168A is parallel to the center axisCL of the disaggregation chamber 125 (i.e., the exit angle is about 90degrees). By having an exit angle of less 105 degrees (or at about 90degrees), the transition surface 168A advantageously produces a suddenexpansion into the disaggregation chamber 125. Referring to FIG. 29,this arrangement produces a flow separation or disruption ofrecirculating rotational flow when a second portion A2 of the inletairflow is conveyed from the intake channel 160A to the chamber 125. Insome embodiments, the flow separation can produce recirculation of thesecond portion A2 of the inlet airflow or can otherwise cause the secondportion A2 of the inlet airflow to be disrupted or “fan out” in one ormore directions that are not tangential to the chamber wall, as shown bythe arrows A2 in FIG. 29. This arrangement produces improveddisaggregation of the dry powder and mixing of the particles within theairflow.

Referring to FIG. 27, in some embodiments, the termination edge (theintersection of the termination surface 168A and the inner surface 151)can be a substantially sharp edge (e.g., have an edge radius of lessthan about 50 microns). This can further enhance flow separation as thesecond portion of the inlet airflow is conveyed through the intake port165A and into the disaggregation chamber. In some embodiments, theinclusion of sharp edges that bound the intake port 165A (or any of theexit openings described herein) produces a flow separation when the airflow is conveyed from the inlet passageway to the chamber 125. Thisproduces a more dispersed or “fanned-out” air jet within the chamber125, which can facilitate mixing. In other embodiments, however, theedge between the transition surface 168A and the inner surface 151 canbe curved or have a radius of greater than about 50 microns (i.e., caninclude an edge break). In other embodiments, the termination edges canbe curved, radiused, interrupted (i.e., can include an edge break), orthe like.

The exit ramp 167A is the side wall that forms the end portion of theinlet passageway 160A and the boundary of a portion of the intake port165A. The exit ramp 167A is a curved surface (i.e., a continuous,non-linear surface). The curved shape of the exit ramp 167A results in amore gradual (or smoother) exit from this portion of the intake port165A. In some embodiments, the exit ramp 167A can be curved in multipledimensions as described herein. Although the termination surface 168Aand the exit ramp 167A are described with respect to the intake port165A, any of the intake ports described herein can include similarstructure. Moreover, although the exit ramp 167 is described as beingcurved or non-linear, in other embodiments, the exit ramp 167 can be alinear “ramped” surface and/or can include linear portion.

The exit portion 170 of the upper member 150 includes a top surface 171and a curved, distal edge 183. The curved distal edge 183 is alignedwith (or mates with) the distal edge 143 of the lower portion 120 todefine the distal end portion (or mouthpiece) of the device 100. Theexit portion 170 defines a central exit opening 156, an exit passageway174 (see FIG. 15) and two bypass passageways (see e.g., passageway 175Ain FIG. 16). The curved distal edge 183 defines the exit opening 178through which the inlet air entrained with the medicament particles isconveyed. Specifically, in use air is drawn from the chamber 125, 155,through the central exit opening 156 and into the exit passageway 174,as shown by the arrow DD in FIG. 15. The airflow, entrained withmedicament particles enters into the exit opening 156 via asubstantially cylindrical flow area (or shroud) defined between theinner surface 151 of the upper member 150 and the raised surface 126 ofthe lower member 120. This flow path produces additional dynamic flowpatterns that facilitate further disaggregation of the medicamentparticles.

As described herein, the dry powder P can also include any suitableexcipient, such as, for example, lactose. The dry powder P can ofteninclude predominantly the excipient with a small percentage of the massbeing the API (e.g., one to ten percent). Thus, the deliverycharacteristics of the device 100 can be dependent on the lactosecharacteristics (or the grade of lactose included within the dry powderP). For example, some dry powder P can include a non-sieved lactose witha mean diameter of 60 microns. Such powder formulations thereforeinclude the fine lactose particles (e.g., 1-5 microns), and thus can bemore “sticky” than those formulations that do not include as much of thefine particles. The advantage of using such non-sieved lactose is that ahigher percentage of fine particles can be delivered, which can bebeneficial for the desired treatment (e.g., deep lung delivery or thelike). Such non-sieved formulations, however, can require more turbulentairflow to disaggregate the stickier fine particles than is needed for asieved formulation. Thus, the transition surface 168 and the exit angle⊖ can be optimized for use with (and can provide the desired amount ofdisruptive airflow) for a non-sieved formulation. Thus, in someembodiments, the dry powder P can include a non-sieved lactoseformulation having a mean particle diameter of 60 microns. In otherembodiments, the dry powder P can include a sieved lactose formulationhaving an initial mean particle diameter of 60 microns, but with asubstantial amount of the fine particles removed by the sieve operation.

As shown in FIGS. 13, 15, and 26C, the inner surface 151 of the uppermember includes two protrusions 157 that are positioned adjacent theexit opening 156. When the device 100 is in its assembled configuration,the two protrusions 157 contact the raised surface 126. This arrangementmaintains a constant distance between the exit opening 156 and theraised surface 126, thereby producing a consistent flow area during use,as well as a gap within which the strip 110 can reside without beingpinched between the first member 120 and the second member 150. Forexample, the contact between the protrusions 157 and the raised surface126 prevents deflection of the upper member 150, for example, if theuser squeezes the device 100 during use. Such undesirable deflectioncould, for example, reduce the flow air thereby choking the flow orotherwise decreasing the flow within the chamber 125. Similarly stated,in some embodiments, the annular “air gap” defined between the raisedsurface 126 and the exit opening 156 can be an air flow constrictionpoint, which can generate particle collisions (and disaggregation).Maintaining the constant distance during use (and between varioususers), as described herein, facilitates a consistent air flowresistance during use. This, in turn, improves dose delivery consistencyand maintains a consistent air flow resistance level experienced by thepatient. Thus, the protrusion 157 provides for a more consistent,repeatable delivery of the medicament.

The two bypass passageways (see e.g., passageway 175A in FIG. 16)provide a flow path through which a portion of the air produced byinspiration flows outside of the chamber 125, 155 (see also the arrow EEin FIG. 16). Specifically, the exit portion 170 defines the bypasspassageway 175A that receives bypass air via the bypass inlet 176A (seeFIG. 10) and the bypass passageway that receives bypass air via thebypass inlet 176B (see FIG. 10). As shown in FIG. 9, the curved distaledge 183 defines the bypass openings 177A, 177B through which the bypassair flows from the bypass passageways and into the user's mouth. Thebypass passageways can be sized (or tuned) to manipulate the air flowresistance through the chamber 125.

The medicament delivery device 100 can be used to treat any number ofindications, including asthma and chronic obstructive pulmonary disease(COPD). In use, the user first removes any packaging or overwrap (notshown, but which can be similar to the protective overwrap 711 shown anddescribed below) from about the device 100. The user then removes thestrip 110 by pulling the strip as shown by the arrows in FIG. 25. Asdescribed above, the inclusion of the recess 136 and the strip guidewalls 137 allows portions of the strip 110 to become compressed together(or bunched up) if pulled slightly to one side or the other (i.e., ifpulled in a direction that is not parallel to a longitudinal axis of thestrip 110). This bunching will provide a region of increased strength,thereby allowing the strip 110 to be successfully removed from thedevice 100 without tearing or breaking. Similarly stated, the recess 136and strip guide wall 137 provide a volume that does not pinch, bind, orotherwise promote tearing of the strip 110 during removal.

After the strip 110 is removed, the user then places the distal endportion (or mouthpiece) of the assembled device 100 into their mouth.The user then inhales, which draws air into the two bypass inletopenings 176A, 176B, and also the four external openings 163A, 163B,163C, 163D. As described above, the portion of the air that is drawnthrough the four external openings 163A, 163B, 163C, 163D (referred toas the inlet airflow) is conveyed into the chamber 125, 155 via therespective inlet air passageways 160A, 160B, 160C, 160D. The structuredefining the intake ports 165A, 165B, 165C, 165D imparts the desiredflow characteristics to the inlet airflow as it enters the chamber 125,155, as described herein. The inlet airflow moves within the chamber 125(see, e.g., FIGS. 28 and 29) and entrains the dry powder medicamentstored therein. Continued dynamic motion of the inlet airflow causesdisaggregation of the particles, thus producing the desired emitted doseand fine particle mass and particle size distribution of dose deliveryto the patient. The inlet airflow, entrained with the medicamentparticles, is then conveyed into the exit passageway 174 via the opening156, as described above.

The chamber 125 and the chamber 155 can be of any suitable size toproduce the desired airflow and disaggregation properties. For example,although the chamber 125 is shown as being deeper than the chamber 155,in other embodiments, each of the chamber 125 and the chamber 155 canhave any suitable depth and/or diameter to achieve the desired drugdelivery performance. For example, in some embodiments, an upper member(e.g., the upper member 150) can include features that are similar toand/or symmetrical with those features of a mating lower member (e.g.,the lower member 120). For example, in some embodiments an upper membercan include a raised surface, similar to the raised surface 126, thatdefines an opening, similar to the opening 156. In this manner, thecircular shape of the disaggregation chamber can be produced by both theupper member and the lower member. In other embodiments, a ratio betweenthe depth of a chamber defined by an upper member (e.g., chamber 155) tothe depth of a chamber defined by a lower member (e.g., chamber 125) canbe at least 0.75, at least 0.9, or at least 1.0. By producing asubstantially symmetrical design (e.g., a ratio of about 1.0), thedevice can produce the desired airflow entrained with medicamentparticles independently of the orientation of the device. Similarlystated, this arrangement can produce substantially the same drugdelivery characteristics whether the device is used with the uppermember (e.g., the upper member 150) facing upwards or downwards.

The arrangement of the raised surface 126 and the curved upper chamber155 also limits the likelihood that the powder within the disaggregationchamber 125, 155 will be inadvertently conveyed out of the exit opening156 without being properly disaggregated if the device 100 is tipped orturned upside down during use. Specifically, as described, the dose ofdry powder is delivered via an annular opening between the raisedsurface 126 of the lower member 120 and the surface of the upper member150. The annular opening (or gap) can prevent powder from remaining onthe surface of the upper member 150 if the device 100 is turned upsidedown. The intake channel also limits the likelihood that the powder willexit (or be spilled) backwards out of the dose chamber by including aseries of bends (or a tortuous path).

FIG. 30 is a flow chart of a method 10 of using a dry powder inhaler,according to an embodiment. Although the method 10 is described withreference to the medicament delivery device 100, in other embodiments,the method 10 can be performed using any of the medicament deliverydevices described herein. The method includes moving a strip from afirst position between a first member of a dry powder inhaler and asecond member of the dry powder inhaler to a second position, at 12. Thestrip seals a dry powder within a portion of a disaggregation chamberdefined by a chamber wall of the first member when the strip is in thefirst position. The portion of the disaggregation chamber is in fluidcommunication with an exit channel defined by the second member and anintake channel defined by the second member when the strip is in thesecond position. A mouthpiece of the dry powder inhaler is then placedinto a mouth, at 14.

The method further includes inhaling into the mouth to draw an inletairflow through the intake channel and into the disaggregation chamber,at 16. A portion of the intake channel is shaped and/or positioned suchthat a portion of an inlet airflow has a rotational motion within thedisaggregation chamber. The rotational motion disaggregates the drypowder to produce respirable particles within the rotational airflow.The intake channel and the exit channel are collectively configured toproduce an exit airflow containing the respirable particles for at leasttwo seconds.

In some embodiments, the method 10 optionally includes disposing of thedry powder inhaler, including the first member and the second member, at17. For example, in some embodiments, the dry powder inhaler is a unitdose device, also known as single-use device that is discarded afteruse. In some embodiments, the first member and the second member of thedry powder inhaler are monolithically constructed from a degradablematerial, such as, for example, a degradable material that isbiodegradable, degradable via exposure to ultraviolet radiation, ordegradable, fragmentable, compostable via exposure to any combination ofultraviolet light radiation, oxygen, moisture and biological organisms.Such material can limit possible issues with discarding the single-usedevice.

The medicament delivery device 100 (and any of the medicament deliverydevices or drug products described herein) can be produced using anysuitable method of assembly or manufacturing. For example, FIG. 31 isflow chart of a method 20 of assembling a dry powder inhaler, accordingto an embodiment. Although the method 20 is discussed with reference toFIGS. 18-23 (and the medicament delivery device 100 shown therein), inother embodiments the method 20 can be used to assembly any suitabledevice (drug product).

The method optionally includes opening a monolithically constructeddevice having a first member and a second member joined by a livinghinge to expose a disaggregation chamber defined by the first member, at21. The method includes conveying a dry powder into a portion of adisaggregation chamber defined by a first member of a medical device, at22. Referring to FIG. 18, the dry powder is conveyed into thedisaggregation chamber 125 when the device is in the openedconfiguration. The dry powder can be conveyed using any suitable method,such as, for example, drum filling or a dosator. In some embodiments,the dry powder can be conveyed using any of the methods or structureshown and described in U.S. Pat. No. 9,446,209, entitled “Dry PowderInhalation Device,” which is incorporated herein by reference in itsentirety. In some embodiments, the dry powder can be in the form of acompressed plug of material. In such embodiments, the disaggregationchamber (or the first member 120) can include a target surface (orspace) for placement of the compressed plug during the fill process. Inaddition to the open space shown within the disaggregation chamber 125(see FIG. 13), alternative examples of target surfaces (or spaces) areshown in FIGS. 47-49 below. Such target surfaces can include anindentation, cut-out or other surface treatment to facilitate placingthe dry powder in the desired location within the disaggregationchamber.

After the dry powder is in the disaggregation chamber, a strip (e.g.,the strip 110) is coupled to an inner surface 121 of the first member120 to seal the dry powder within the portion of the disaggregationchamber, at 24. The strip can be spot sealed to the inner surface 121,as shown in FIG. 19, to produce a seal around the disaggregation chamber125. Referring to FIG. 20, the second member 150 of the medical deviceis then placed in contact with the first member 120 such that an innersurface 151 of the second member covers the portion of thedisaggregation chamber 125, at 26. As shown, the second member definingan intake channel and an exit channel The exit channel is configured tobe fluidically coupled to the disaggregation chamber via an exit openingdefined by the inner surface of the second member. The intake channel isconfigured to be fluidically coupled to the disaggregation chamber viaan intake port. As shown in FIG. 19, in some embodiments, the firstmember 120 and the second member 150 are monolithically constructed, andthe second member 150 is placed about the first member 120 by bending aliving hinge 138 between the first member and the second member.

The method 20 further includes deforming a flange (e.g., the flanges144) extending from the inner surface of the first member to be matinglycoupled to a joint surface (e.g., the joint surface 186) of the secondmember to form a sealed joint between the first member and the secondmember, at 28. In some embodiments, the flange can be deformed by heatswaging or heat staking the flange to bend the flange against the jointsurface. Such methods of assembly can limit potential adverse effects onthe powder that may results from high temperatures or other methods ofjoining (e.g., ultrasonic welding, radio frequency welding, or thelike). Such methods are also easy to implement, thereby reducing thecost and complexity of producing the medical device. The heat swagejoining method is beneficial for reducing air leakage variability at theinhaler joints without using ultrasonic welding which can be detrimentalto the powder (high frequency vibration). Other joining methods such assnap fits require air gaps to reliably join given part tolerances, whichleads to air leakage variability.

Referring to FIGS. 22 and 23, the heat swage flanges 144 are part of thelower portion of the inhaler and the mating joint surfaces 186 arelocated on the upper portion of the inhaler. FIG. 23 is a close up viewof the top portion of the inhaler showing the flanges 144 in thedeformed position to form the joint. As shown, in some embodiments, theupper portion 150 can include a set of triangular crush ribs 187designed to block air flow leakage through the gap along the heat swagejoint. In this manner, when a user inhales into the mouthpiece, and flowpath along the exterior of the inhaler (e.g., caused by the gap alongthe joint) will be blocked by the crush ribs 187. This ensures that thefull amount of inspiration is drawing through the mouthpiece, asintended.

Although the drug product 100 is shown as including a series of inletpassageways (e.g., inlet passageway 160A) that include curved exit ramp(e.g., the exit ramp 167A) into the chamber 125, in other embodiments,any of the devices and/or drug products described herein can have anysuitable exit wall structure. For example, although the drug product 100is shown as including a series of intake ports (e.g., intake port 165Aand 165B) defined by a ramp that include vertical (or sharp) transitionsurfaces (e.g., the transition surfaces 168A, 168B) into the chamber125, in other embodiments, any of the devices and/or drug productsdescribed herein can have an exit wall structure that gradually leads(or diffuses) into the chamber (e.g., the chamber 125 or any similarchambers described herein).

For example, FIGS. 32A, 32B, and 33 show a drug product (or medicamentdelivery device) 800, according to an embodiment. The drug product (ormedicament delivery device) 800 is similar in many respects to themedicament delivery device 100 shown and described herein, and thereforecertain portions of the device 800 are not described in great detail. Asshown, the medicament delivery device 800 defines a series of air inletpassageways, including the air inlet passageway 860B. The deviceincludes an intake ramp 867B that is a gradual transition into thechamber 825. As shown, the intake ramp 867B forms an exit angle ⊖ withrespect to the surface 851 that is greater than 105 degrees. Forexample, in some embodiments, the exit angle ⊖ is about 135 degrees.Similarly stated, the intake ramp 867B causes the flow to turn about 45degrees within the intake channel 860B. This arrangement produces lessdisruptive air jet(s) than those produced with the lower exit angleshown and described above with reference to the device 100. Thus, thehigher exit angle reduces the amount of flow separation, which biasesair/drug flow toward center outlet hole of the dose chamber 825 as flowre-circulates. FIG. 33 is a close-up view of FIG. 32B with the criticalinlet air flow control surface 867 highlighted in bold line weight.Smooth transition air inlets can be beneficial for maximizing particlerotation, increasing dose release time and disaggregation of highlyflowable powders.

As described herein, the dry powder P can also include any suitableexcipient, such as, for example, lactose. The dry powder P can ofteninclude predominantly the excipient with a small percentage of the massbeing the API (e.g., one to ten percent). Thus, the deliverycharacteristics of the device 600 can be highly dependent on the lactosecharacteristics (or the grade of lactose included within the dry powderP). For example, some dry powder P can include a non-sieved lactose witha mean diameter of 60 microns. Such powder formulations thereforeinclude the fine lactose particles (e.g., 1-5 microns), and thus can bemore “sticky” than those formulations that do not include as much of thefine particles. The advantage of using such non-sieved lactose is that ahigher percentage of fine particles can be delivered, which can bebeneficial for the desired treatment (e.g., deep lung delivery or thelike). Such non-sieved formulations, however, can require more turbulentairflow to disaggregate the stickier fine particles than is needed for asieved formulation. Thus, on some embodiments, however, the dry powder Pcan include a sieved lactose formulation having an initial mean particlediameter of 60 microns, but with a substantial amount of the fineparticles removed by the sieve operation. Such embodiments, therefore,may not require the high amount of disruptive airflow delivered by someof the embodiments described herein. Thus, the higher exit angel (e.g.,of greater about 135 degrees) can produce less turbulence and provide asuitable rotational flow for such a sieved formulation.

FIG. 34 shows a medicament delivery device 800′, according to anembodiment. The drug product (or medicament delivery device) 800′ issimilar in many respects to the medicament delivery device 100 or 800shown and described herein, and therefore certain portions of the device800′ are not described in great detail. As shown, the medicamentdelivery device 800′ defines an air inlet passageway 860B′ that includesa vertical channel (or side wall) 868′ into the chamber 825′. The sidewall 868′ includes an abrupt sharp edge at the transition to the dosechamber 825′ to disrupt rotational flow and fan-out flow to enable flowof particles to the air/drug exit opening to improve emitted dosepercentage.

In some embodiments, any of the medicament delivery device (or drugproducts) described herein can have a combination of different inletpassageway geometries and/or different outlet geometries. For example,any of the embodiments described herein can have one or more inletpassageways defined by a vertical wall (as shown by the transitionsurface 168A described above), one or more inlet passageways defined bya gradual wall (as shown by the ramp 867B described above), and/or oneor more inlet passageways defined by a cylindrical sharp wall (as shownby the wall 868′). This can allow the device to be tailored for aspecific drug. Specifically, dry powder drug formulations can varygreatly in term of particle size, cohesiveness, surface attraction andflowability. To achieve the desired drug delivery performance (emitteddose and fine particle fraction) for a specific dry powder drugformulation, combinations of abrupt inlets such as vertical wall andsmooth transition inlets (such as the 135-degree exit angle) may beintegrated into the inhaler design. Using a four-inlet configuration asan example, FIGS. 35A-35C illustrate some of the possible combinations.In some embodiments, an inhaler design may include two or more airinlets with combinations of abrupt and smooth air inlets.

The medicament delivery devices 100′, 100″ and 100′″ shown in FIGS.35A-35C can be similar to the device 100 described above, but includesdifferent intake ports. In referring to FIGS. 35A-35C, the arrows A1represent the recirculating airflow within the disaggregation chamber,the arrows A2 represent straight inlet air produced by a ramp 867B, thearrows A3 represent the deflected (or fanned out) inlet air produced bya ramp 167B, and the arrow Aout represents the flow of air and drug outof the device. FIG. 35A shows a device 100′ including one vertical wallair inlet (identified as a ramp 167B) and three smooth transition airinlets (identified as ramps 867B) into the chamber 125. FIG. 35B shows adevice 100″ including two vertical wall air inlets (identified as ramps167B) and two smooth transition air inlets (identified as ramp 867B)into the chamber 125. FIG. 35C shows a device 100′″ including threevertical wall air inlets (identified as ramps 167B) and one smoothtransition air inlet into the chamber 125 (identified as a ramp 867B).

Although the inlet portion 153 is shown as including four inletpassageways 160A, 160B, 160C, 160D, in other embodiments, the device 100(and any of the devices shown herein) can include any suitable number ofinlet passageways. For example, in some embodiments, a device caninclude two inlet passageways, three inlet passageways, or even morethan four inlet passageways. Moreover, although the inlet passageways160A, 160B, 160C, 160D are shown as having a particular flow geometry,in other embodiments, a device can include any suitable flow geometryfor any of the inlet passageways. For example, in some embodiments, aportion of an inlet passageway can include any suitable curves, radius,or edge designs to facilitate the desired entrainment, disaggregation,and/or production of the dry powder medicament therein.

For example, FIGS. 36 and 37 show a top view and a perspective view,respectively, of a portion of a medicament delivery device (or drugproduct) 200 according to an embodiment. The medicament delivery device200 includes a lower member (or portion) 220 and an upper member (orportion) 250. FIG. 37 shows the lower member 220 and the upper member250 in a substantially planar configuration to clearly show the featuresof each member. In use, the upper member 250 is coupled to the lowermember 220 to form the assembled medicament delivery device 200. Themedicament delivery device 200 is similar in many respects to themedicament delivery device 100 shown and described herein, and thereforecertain portions of the device 200 are not described in great detail.For example, like the device 100, when assembled, the medicamentdelivery device 200 can be similar to, and can include certain featuresof, any of the medicament delivery devices shown and described in U.S.Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which isincorporated herein by reference in its entirety.

The lower member 220 is similar to the lower member 120, and istherefore not described in great herein. Specifically, the lower member220 defines a chamber 225 within which any suitable medicament isstored. In addition to providing a volume or reservoir within which amedicament can be stored, the chamber 225 also functions as a chamber(or a portion of a chamber) within which the medicament can bedisaggregated or otherwise prepared for delivery to a patient.Specifically, the lower member 220 includes a raised central surface226, an outer portion (or wall) 230, and an inner portion (or wall) 234.Together, these structures form a portion of (or define) the chamber225. As described below, in use an inlet air flow can flow in arotational (or swirling manner) within the chamber 225, bounded by theouter wall 230 and the inner wall 234. The chamber 225 can be configuredsuch that, as the medicament is disaggregated into particles within thedesired size range, the particles are entrained in the airflow and exitthe chamber 225 via an exit opening 256 that is spaced apart from (andabove) the raised surface 226.

The upper member 250 includes a first (or inner) surface 251 and asecond (or outer) surface. The inner surface 251 defines a chamber 255that, along with the chamber 225, forms a disaggregation chamber orvolume, as described above. The upper member 250 includes an inletportion 253 and an exit portion. The exit portion of the medicamentdelivery device 200 is similar to the exit portion 170 of the device 100described above, and is therefore not shown or described herein.

The inlet portion 253 differs from the inlet portion 153 of the device100 described above, in that the inlet portion 253 includes differentshapes and geometries associated with the inlet passages. As describedherein, the inlet portion 253 defines a series of inlet passagewaysthrough which inlet air flows into the disaggregation chamber when thepatient inhales through the device 200. As described herein, thecharacteristics of the inlet air flow as it enters the chambers 225, 255can impact the accuracy and repeatability with which the medicamentwithin the chambers 225, 255 is disaggregated, broken up, and/orotherwise prepared for delivery to the patient. For example, the shapeand size of the inlet passageways can influence the airflow patternwithin the chamber 225. The angle of entry, in turn, can impact thenumber of revolutions that entrained particles make within the chamber225 before exiting. Thus, the inlet portion 253 is configured to producethe desired inlet airflow such that the desired exit characteristics(e.g., velocity, flow rate, particle size distribution) are achieved.

In particular, the inlet portion 253 includes four inlet passageways: afirst inlet passageway 260A, a second inlet passageway 260B, a thirdinlet passageway 260C, and a fourth inlet passageway 260D. Referring toFIG. 36, the first inlet passageway 260A includes an external opening263A through which inlet air is drawn from outside of the device 200,and intake port 265A through which the inlet air is conveyed into thechambers 255, 225, and a curved portion therebetween. The second inletpassageway 260B includes an external opening 263B through which inletair is drawn from outside of the device 200, and intake port 265Bthrough which the inlet air is conveyed into the chambers 255, 225, anda curved portion therebetween. The third inlet passageway 260C includesan external opening 263C through which inlet air is drawn from outsideof the device 200, and intake port 265C through which the inlet air isconveyed into the chambers 255, 225, and a curved portion therebetween.The fourth inlet passageway 260D includes an external opening 263Dthrough which inlet air is drawn from outside of the device 200, andintake port 265D through which the inlet air is conveyed into thechambers 255, 225, and a curved portion therebetween.

The exit openings 265A, 265B, 265C, 265D are located on the innersurface 251 such that they open in to (or are in fluid communicationwith) the chamber 225 after the removal of any partition or seal that isdisposed about the chamber 225. In this manner, upon inspiration(inhalation) by the patient, air is drawn from outside of the devicethrough the external openings 263A, 263B, 263C, 263D, within the variouscurved portions of each of the inlet passageways, and into the chamber225 via the intake ports 265A, 265B, 265C, 265D. As described above, theinlet passageways 260A, 260B, 260C, 260D can include any suitablegeometry or size to produce the desired airflow characteristics withinthe chamber 225. For example, as shown in FIG. 37, the intake port 265Acan be defined and/or bounded by a termination edge 266A and an exitramp 267A. In contrast to the termination edge 166A (which is a linearedge), the termination edge 266A is a curved edge that intersects thechamber 225, and provides structure that directs the inlet air flow whenexiting the inlet passageway 260A. Specifically, the termination edge266A is formed by the intersection of the inner surface 251 and the sidewall that defines a portion of the inlet passageway 260A.

The exit ramp 267A is the side wall that forms the end portion of theinlet passageway 260A and the boundary of a portion of the intake port265A. The exit ramp 267A is a curved surface (i.e., a continuous,non-linear surface) that terminates, like the termination edge 266A, ina sharp edge. Unlike the termination edge 266A, however, the curvedshape of the exit ramp 267A results in a more gradual (or smoother) exitfrom this portion of the intake port 265A. Although the termination edge266A and the exit ramp 267A are described with respect to the intakeport 265A, any of the exit openings described herein can include similarstructure.

In some embodiments, the curved termination edge 266A and/or the curvedexit ramp 267A can direct the inlet air flow entering the chamber 225toward the outer portion (or wall) 230. Because the powder circulationis biased more toward the outer wall 230 of the dose chamber 225, thedisaggregated particles within the airflow then flow through and aroundthese biased air inlet jets prior to exiting the chamber 225 via theexit opening 256. This arrangement can cause a portion (similar to thesecond portion A2 shown in FIG. 5) of the inlet airflow to be conveyedoutwardly towards the chamber wall 230. In this manner, the rotationalflow within the disaggregation chamber 225 is biased towards anddeflects off the outside portion of the disaggregation chamber 225,toward the exit opening 256. Similarly stated, the portion of theairflow can “bounce” off the outer portion of the wall 230 and beconveyed through the primary circulating airflow (similar to the firstportion A1 shown in FIG. 5) and toward the exit opening 726. Thus, theparticles circulating within the primary airflow will flow through (andbe disrupted by) a portion of the inlet airflow. In this manner, theflow pattern of the inlet air entering the chamber 225 can affect thedelivery of the disaggregated medicament. In some embodiments, forexample, this arrangement can be advantageous for the delivery ofcohesive powders with poor flowability. Similarly stated, thisarrangement can help “speed up drug release to the patient, for example,by forcing the powder medicament to exit the device 200 in a shorterperiod of time. For example, if the patient inhales for four seconds, itmay be desirable to release the powder over a two second period of time,rather than a 4 second delivery time. Releasing the powder medicament ata faster rate means fast and efficient powder clearance from the dosechamber, and therefore potentially results in higher emitted dosepercentage and more consistent dosing (dose-to-dose uniformity). Bydelivering a consistent dose with adequate particle size distribution,the drug product can be tailored to match marketed drug products. Forexample, in some embodiments, the drug product 200 (or any other drugproducts described herein) can produce a particle size distribution wellsuited for reaching the deeper areas (e.g., alveoli) of the lungs.

FIG. 38 depicts an inhaler 200′ with ‘outside radius air inlets’ havingdifferent sizes. Specifically, the inhaler includes radiused terminationedges 266A, 266B, 266C and 266D that are radiused or ramped air inletsof variable size to guide powder more directly to the outlet in a swirlflow pattern.

Although shown as being circular in shape, in other embodiments, thechamber 125 (or any of the dose or disaggregation chambers describedherein) can have any suitable shape and/or can include any suitable flowstructures therein to promote the desired preparation of the medicamentfor delivery via inhalation.

For example, FIGS. 39 and 40 are top views of a portion of a medicamentdelivery device (or drug product) 300 according to an embodiment. FIG.39 shows the device 300 in an opened configuration and FIG. 40 shows thedevice in a closed configuration. The medicament delivery device 300includes a lower member (or portion) 320 and an upper member (orportion) 350. FIG. 39 shows the lower member 320 and the upper member350 in a substantially planar configuration to clearly show the featuresof each member. In use, however, the upper member 350 is coupled to thelower member 320 to form the assembled medicament delivery device 300,as shown in FIG. 40. The medicament delivery device 300 is similar inmany respects to the medicament delivery device 100 and/or themedicament delivery device 200 shown and described herein, and thereforecertain portions of the device 300 are not described in great detail.For example, like the devices 100, 200, when assembled, the medicamentdelivery device 300 can be similar to, and can include certain featuresof, any of the medicament delivery devices shown and described in U.S.Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which isincorporated herein by reference in its entirety.

The upper member 350 is similar to the upper member 150 shown anddescribed above. Specifically, the upper member 350 defines a chamber355 that, along with the chamber 325, forms a disaggregation chamber orvolume, as described above. The upper member 350 includes an inletportion 353 that includes four inlet passageways: a first inletpassageway 360A, a second inlet passageway 360B, a third inletpassageway 360C, and a fourth inlet passageway 360D. The first inletpassageway 360A includes an external opening through which inlet air isdrawn from outside of the device 300, and an intake port 365A throughwhich the inlet air is conveyed into the chambers 355, 325. The secondinlet passageway 360B includes an external opening through which inletair is drawn from outside of the device 300, and an intake port 365Bthrough which the inlet air is conveyed into the chambers 355, 325. Thethird inlet passageway 360C includes an external opening through whichinlet air is drawn from outside of the device 300, and an intake port365C through which the inlet air is conveyed into the chambers 355, 325.The fourth inlet passageway 360D includes an external opening throughwhich inlet air is drawn from outside of the device 300, and an intakeport 365D through which the inlet air is conveyed into the chambers 355,325.

The intake ports 365A, 365B, 365C, 365D are located such that they openin to (or are in fluid communication with) the chamber 325 after theremoval of any partition or seal that is disposed about the chamber 325.The intake ports 365A, 365B, 365C, 365D are shown on the lower member320 to identify their location when the device 300 is in the assembledconfiguration. In this manner, upon inspiration (inhalation) by thepatient, air is drawn from outside of the device through the externalopenings, within the various curved portions of each of the inletpassageways, and into the chamber 325 via the intake ports 365A, 365B,365C, 365D. As described above, the inlet passageways 360A, 360B, 360C,360D can include any suitable geometry or size to produce the desiredairflow characteristics within the chamber 325.

The lower member 320 defines a chamber 325 within which any suitablemedicament is stored. In addition to providing a volume or reservoirwithin which a medicament can be stored, the chamber 325 also functionsas a chamber (or a portion of a chamber) within which the medicament canbe disaggregated or otherwise prepared for delivery to a patient.Specifically, the lower member 320 includes a raised central surface326, an outer portion (or wall) 330, and an inner portion (or wall) 334.Together, these structures form a portion of (or define) the chamber325.

The lower member 320 differs from the lower member 120 in that the lowermember 320 includes a series of ramps 331. Each ramp 331 is locatedadjacent to the region at which the inlet air flow is conveyed from theintake ports 365A, 365B, 365C, 365D into the chamber 325. In thismanner, the ramps 331 can obstruct any “dead zones” or low flow velocityeddy currents within the chamber 325, thereby promoting improved mixing,flow properties and more complete dose delivery from the disaggregationchamber. Similarly stated, the ramps 331 can direct the flow from oneintake port (e.g., intake port 365A) away from (or out of the path from)an adjacent intake port (e.g., intake port 365B) and toward center toassist clearance of particles from the disaggregation chamber (flow tooutlet opening).

FIG. 41 is a top view of a portion of a medicament delivery device (ordrug product) 400 according to an embodiment. The medicament deliverydevice 400 includes a lower member (or portion) 420 and an upper member(or portion) 450. FIG. 41 shows the lower member 420 and the uppermember 450 in a substantially planar configuration to clearly show thefeatures of each member. In use, however, the upper member 450 iscoupled to the lower member 420 to form the assembled medicamentdelivery device 400. The medicament delivery device 400 is similar inmany respects to the medicament delivery device 100 and/or themedicament delivery device 200 shown and described herein, and thereforecertain portions of the device 400 are not described in great detail.For example, like the devices 100, 200, when assembled, the medicamentdelivery device 400 can be similar to, and can include certain featuresof, any of the medicament delivery devices shown and described in U.S.Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which isincorporated herein by reference in its entirety.

The upper member 450 is similar to the upper member 150 shown anddescribed above. Specifically, the upper member 450 defines a chamber455 that, along with the chamber 425, forms a disaggregation chamber orvolume, as described above. The upper member 450 includes an inletportion 453 that includes four inlet passageways: a first inletpassageway 460A, a second inlet passageway 460B, a third inletpassageway 460C, and a fourth inlet passageway 460D. The first inletpassageway 460A includes an external opening through which inlet air isdrawn from outside of the device 400, and intake port 465A through whichthe inlet air is conveyed into the chambers 455, 425. The second inletpassageway 460B includes an external opening through which inlet air isdrawn from outside of the device 400, and intake port 465B through whichthe inlet air is conveyed into the chambers 455, 425. The third inletpassageway 460C includes an external opening through which inlet air isdrawn from outside of the device 400, and intake port 465C through whichthe inlet air is conveyed into the chambers 455, 425. The fourth inletpassageway 460D includes an external opening through which inlet air isdrawn from outside of the device 400, and intake port 465D through whichthe inlet air is conveyed into the chambers 455, 425.

The intake ports 465A, 465B, 465C, 465D are located such that they openin to (or are in fluid communication with) the chamber 425 after theremoval of any partition or seal that is disposed about the chamber 425.The intake ports 465A, 465B, 465C, 465D are shown on the lower member420 to identify their location when the device 400 is in the assembledconfiguration. In this manner, upon inspiration (inhalation) by thepatient, air is drawn from outside of the device through the externalopenings, within the various curved portions of each of the inletpassageways, and into the chamber 425 via the intake ports 465A, 465B,465C, 465D. As described above, the inlet passageways 460A, 460B, 460C,460D can include any suitable geometry or size to produce the desiredairflow characteristics within the chamber 425.

The lower member 420 defines a chamber 425 within which any suitablemedicament is stored. In addition to providing a volume or reservoirwithin which a medicament can be stored, the chamber 425 also functionsas a chamber (or a portion of a chamber) within which the medicament canbe disaggregated or otherwise prepared for delivery to a patient.Specifically, the lower member 420 includes a raised central surface426, an outer portion (or wall) 430, and an inner portion (or wall) 434.Together, these structures form a portion of (or define) the chamber425.

The lower member 420 also includes a series of vanes (also referred toas ridges or partitions) 431. Each vane 431 is located adjacent to theregion at which the inlet air flow is conveyed from the intake ports465A, 465B, 465C, 465D into the chamber 425. In this manner, the vanes431 can direct the flow entering the chamber 425, thereby promotingimproved mixing, flow properties and more complete dose delivery fromthe disaggregation chamber. Specifically, the vanes 431 can divide eachjet of inlet air into a first portion that is directed towards innerwall 434 (see the arrow EE) to assist in clearance of particles from thedisaggregation chamber (flow to outlet hole) and a second portion thatis directed towards outer wall promote disaggregation of particles 430(see the arrow FF).

Although the device 100 is shown as including two protrusions 157 thatcontact the raised surface 126, in other embodiments, a device caninclude any suitable type of flow structures, stiffeners or the like inthe region surrounding the exit opening and/or the raised surface. Forexample, FIG. 42 is a top view of a portion of a medicament deliverydevice (or drug product) 500 according to an embodiment. The medicamentdelivery device 500 includes a lower member (or portion) 520 and anupper member (or portion) 550. FIG. 42 shows the lower member 520 andthe upper member 550 in a substantially planar configuration to clearlyshow the features of each member. In use, however, the upper member 550is coupled to the lower member 520 to form the assembled medicamentdelivery device 500. The medicament delivery device 500 is similar inmany respects to the medicament delivery device 100 and/or themedicament delivery device 200 shown and described herein, and thereforecertain portions of the device 500 are not described in great detail.For example, like the devices 100, 200, when assembled, the medicamentdelivery device 500 can be similar to, and can include certain featuresof, any of the medicament delivery devices shown and described in U.S.Pat. No. 9,446,209, entitled “Dry Powder Inhalation Device,” which isincorporated herein by reference in its entirety.

The upper member 550 is similar to the upper member 150 shown anddescribed above. Specifically, the upper member 550 defines a chamber555 that, along with the chamber 525, forms a disaggregation chamber orvolume, as described above. The upper member 550 includes an inletportion that includes four inlet passageways: a first inlet passageway560A, a second inlet passageway 560B, a third inlet passageway (notshown), and a fourth inlet passageway 560D.

The exit openings of the inlet passageways are located such that theyopen in to (or are in fluid communication with) the chamber 525 afterthe removal of any partition or seal that is disposed about the chamber525. In this manner, upon inspiration (inhalation) by the patient, airis drawn from outside of the device through the external openings,within the various curved portions of each of the inlet passageways, andinto the chamber 525, as described above.

The lower member 520 defines a chamber 525 within which any suitablemedicament is stored. In addition to providing a volume or reservoirwithin which a medicament can be stored, the chamber 525 also functionsas a chamber (or a portion of a chamber) within which the medicament canbe disaggregated or otherwise prepared for delivery to a patient.Specifically, the lower member 520 includes a raised central surface526, an outer portion (or wall) 530, and an inner portion (or wall) 534.Together, these structures form a portion of (or define) the chamber525.

The lower member 520 also includes a series of protrusion (also referredto as posts) 531 (only one of the six protrusions is labeled). Theprotrusions 531 are located surrounding the raised central surface 526.Specifically, FIG. 43 shows a side view showing the protrusions. In thismanner, the protrusions 531 can direct the flow exiting the chamber 525,thereby promoting improved mixing and flow properties. Specifically, theprotrusions 531 can control the exit flow rate of the medicament bydeflecting outgoing particles, enhance the deflection of the dry powder(to improve disaggregation) and/or produce more rotation or flow eddies(to improve disaggregation).

Although the protrusions 531 are shown as being on the lower member, inother embodiments, the protrusions can be on either, the lower member,the upper member, or both. For example, FIG. 44 shows a device 500′including protrusions 531′ on both the lower member and the uppermember.

Although shown as having a circular cross-sectional shape, in otherembodiments, the protrusions 531 can have any suitable shape. Forexample, in some embodiments, the protrusions 531 can be rectangular,octagonal, or any other suitable polygon shape. For example, FIGS. 45and 46 show a device 500″ including protrusions 531″ having a teardropshape with flat powder control surface. FIG. 47 shows a device 500′″including protrusions 531′″ having a modified teardrop shape to deflectthe flow inward in a different manner Moreover, although the raisedcentral surface 126 is shown as being substantially flat (or planar), inother embodiments, the raised central surface of any embodimentsdescribed herein can have any suitable shape. For example, the raisedcentral surface 526 can be a convex shape, a concave shape, a sphericalshape, or the like.

Although the chamber 125 and the chamber 155 are each shown anddescribed has having circular cross-sectional shape, in otherembodiments, any of the chambers described herein can have any suitableshape. For example, FIGS. 48-50 show schematic illustrations of chambershaving non-circular cross-sectional shapes with constriction andexpansion areas for rotational flow, and outlets located to pick up fineparticles. Specifically, FIG. 48 shows a chamber 625 having targetlocations 622 and FIG. 49 shows a chamber 625′ having target locations622′. FIG. 50 shows a chamber 625″ having a single target location 622″.As described above, the target locations are areas of the chamber thatcan receive a compressed plug of dry powder. The arrows representvarious flow patterns that are facilitated by and/or produced within thechambers.

Although the device 700 and the device 200 are shown and described asincluding an intake ramp (e.g., the ramp 767 and the ramp 267A) thatinclude a curved surface, in other embodiments, a device can include anintake ramp that includes multiple curved surfaces. For example, FIG. 51is a schematic illustration of a medicament delivery device (or drugproduct) 700′ according to an embodiment. The medicament delivery device700′ is similar to the medicament delivery device (or drug product) 700described above, and is therefore not described in detail herein.Specifically, the device 700′ includes an intake channel 760′ that isconfigured to be fluidically coupled to the disaggregation chamber 725′via an intake port 765′. The intake port 765′ is defined at least inpart by an intake ramp 767′ that is curved both outwardly towards thechamber wall and inwardly towards the exit opening. This arrangementcreates and narrow tipped opening at the inlet/chamber transition to“nozzle” the inlet flow (i.e., to produce a higher velocity in the inletflow) downward to disrupt the rotational flow and deflect powder Ptoward the exit opening 756′, as shown by the arrows.

Any of the medicament delivery devices (drug products) described hereincan be included within any suitable packaging. For example, FIG. 50depicts a packaging assembly that contains an inhaler 707 therein. Theinhaler 707 can be similar to any of the devices shown and describedherein, such as the medicament delivery device 100, and includes anactivation trip (pull tab) 708 sealed inside a protective overwrap 711for protection from ultraviolet light and moisture. The overwrap 711 isheat sealed 709 on all sides and includes a slit 710 for easy opening.In some embodiments, the overwrap can be injected and sealed with aninert gas to ensure that the powder (e.g., drug, nutraceuticals)contained in the inhaler 707 is not stored in an environment includingoxygen.

In addition to the concept shown in FIG. 50, the activation trip (pulltab) 708 may be sealed between the layers of the overwrap 711 as shownin FIG. 51. In this embodiment, the user can tear or peel open theoverwrap 711 at the slit 710 location, and remove the inhaler 707 fromthe overwrap 711. Since the activation strip (pull tab) 708 is sealed tothe overwrap, the activation strip (pull tab) 708 would be removed fromthe inhaler as the inhaler 707 as its pulled out of the overwrap 711.This packaging design eliminates one user operational step to simplifyuse and administration.

In some embodiments, a kit includes a package containing a dry powderinhaler and an applicator. The dry powder inhaler is configured todeliver a unit dose of a dry powder medicament. The applicator isconfigured to be removably coupled to the dry powder inhaler and allowsa caregiver to position the dry powder inhaler for a user withouttouching the patient or the dry powder inhaler. In this manner, theapplicator facilitates maintaining sterility during drug delivery. Forexample, any of the inhalers described herein may be administered to thepatient with use of a wand or holder to help prevent cross contaminationfrom the patient to nurse or caregiver. The wand would clamp onto theinhaler at the rear non-patient contact end and after dose delivery ahand grip located trigger release would be activated for ejection fromthe wand and disposal of the spent single use inhaler.

Compositions

In some embodiments, any of the medicament delivery devices describedherein can include any suitable medicament, nutraceutical, orcomposition. In some embodiments, any of the medicament delivery devices(or drug products) described herein can include a composition includingany suitable active pharmaceutical ingredient (API), any suitableexcipient, bulking agent, carrier particle, or the like.

In some embodiments, the API can include albuterol sulfate (alsoreferred to as “sulphate,” for example, in Europe). In otherembodiments, any of the drug products described herein can include anyother bronchodilator. For example, in some embodiments the API caninclude a short-acting bronchodilator, such as, for example,levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, and/orfenoterol. For example, in some embodiments the API can include along-acting bronchodilator, such as, for example, aclidinium (Tudorza),arformoterol (Brovana), formoterol (Foradil, Perforomist),glycopyrrolate (SeebriNeohaler), indacaterol (Arcapta), olodaterol(Striverdi Respimat), salmeterol (Serevent), tiotropium bromide(Spiriva), umeclidinium (IncruseEllipta), mometasone furoate powder,flunisolide, budesonide, and/or vilanterol.

In some embodiments, the API included in any of the drug productsdescribed herein can include methylxanthines or theophylline.

In some embodiments, the API included in any of the drug productsdescribed herein can include a combination drug. Such combination drugscan be, for example, a combination of either of two long-actingbronchodilators or of an inhaled corticosteroid and a long-actingbronchodilator. Suitable combination drugs includeglycopyrrolate/formoterol (Bevespi Aerosphere),glycopyrrolate/indacaterol (UtibronNeohaler), tiotropium/olodaterol(StioltoRespimat), umeclidinium/vilanterol (AnoroEllipta),budesonide/formoterol (Symbicort), fluticasone/salmeterol (Advair),fluticasone/vilanterol (BreoEllipta). Although listed as including“double” combinations, in other embodiments, a drug product describedherein can include triple (or quadruple) combinations.

In some embodiments, the API included in any of the drug productsdescribed herein can include Roflumilast.

In some embodiments, the API included in any of the drug productsdescribed herein can include a salt or ester such as sulfate (sulphate),or propionate or bromide.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable SABA (short actingbeta-agonist), LABA (long acting beta-agonist), LAMA (long actingmuscarinic agent), SAMA (short acting muscarinic agent), or ICS (inhaledcorticosteroid). For example, inhaled corticosteroids can include any ofthe corticosteroids described herein (e.g., flunisolide), as well asothers, including fluticasone, mometasone, ciclesonide, orbeclomethasone.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled anti-infectivecomposition. Such compositions can include, for example, ribavirin,tobramycin, zanamivir, pentamidine, gentamicin, cidofovir, or anycombination of these.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled antibiotic and/orantiviral composition. Such compositions can include, for example,antibiotics used to treat tularemia, including streptomycin, gentamicin,doxycycline, and ciprofloxacin. Such compositions can include, forexample, antibiotics used to treat inhalational anthrax. Considerableprogress in finding new drugs and suitable therapy for treatment ofanthrax has been achieved, and such compositions can includelevofloxacin, daptomycin, gatifloxacin, and dalbavancin. Suchcompositions can include, for example, antivirals to treat or preventinfluenza (i.e. Relenza-zanamivir—5 mg doses), antivirals used to treatadenovirus pneumonia (e.g., brincidofovir), antivirals to treat RSV(e.g., Ribavirin).

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled composition forpatients with cystic fibrosis. Such compositions can include, forexample, tobramycin, aztreonam, colistin, mannitol, or pulmozyme.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled vaccine. Such vaccinesinclude, for example, influenza vaccines, tuberculosis vaccines, malariavaccines, or any other vaccine suitable for delivery in an inhaledpowder form.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable composition for treatingmigraine headaches. Such compositions include, for example,Dihydroergotamine, Imitrex, sumatriptan, Maxalt, Relpax, Amerge, Axert,Butalbital compound, Zomig, Cambia, Treximet, Excedrine, Fiorinal,rizatriptan, gabapentin, Frova, Reglan, cyclobenzaprine, naratriptan,Norflex, diclofenac, and Methergine.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled medicament fortreating anaphylaxis, croup, asthma, or the like. Such compositions caninclude a local anesthetic. Such compositions can include epinephrine.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled proteins and peptides.Such compositions can include, for example, insulin.

In some embodiments, the API included in any of the drug productsdescribed herein can include any suitable inhaled medicaments forbiodefense (i.e., antidote treatment nerve agents). Such compositionscan include, for example, Atropine or Atropine Sulfate, Pralidoxime, acombination of Atropine and Pralidoxime, Diazepam. Such compositions canbe included to treat any indication, such as for use as a sedative totreat anxiety, muscle spasms, and seizures.

In some embodiments, the API included in any of the drug productsdescribed herein can include loxapine, alprazolam, fentanyl, orzaleplon.

Suitable excipients can include any composition or additive that form,along with the API, the desired formulation for filling, long termstorage, delivery to the target location, or the like. Examples ofsuitable excipients include lactose, magnesium stearate, magnesiumstearate-treated lactose carrier particles, trehalose, any sugars foruse as cryoprotectants (e.g., mannitol), compositions used as solubilityenhancers (e.g., cyclodextrine), and any combination of the above,including double, triple, or any other combination(s).

In some embodiments, the composition included in any of the drugproducts described herein can include any suitable naturally-occurringcomposition, such as nicotine, cannabinoids, or the like.

The drug product 100 (and any of the drug products described herein) canhave any suitable size (e.g., length, width and/or depth) and cancontain any suitable volume (or dose amount) of the medicament. In thismanner, the chamber 125 (or any chambers described herein) can beconfigured to provide a desired fill volume and/or weight, and emitteddose (mass). In some embodiments, for example, the volume of the chamber125 (or any chamber described herein) can be such that the fill weightof the composition is approximately 10 mg and the delivery amount of thecomposition is approximately 10 mg (providing an emitted dose percentageof approximately 85 percent). In other embodiments, however, the dosesize (or weight) can range from 5 mg to 50 mg.

The fill weight and/or delivered dose (mass) can be adjusted such thatany of the drug products described herein can include and/or deliver asuitable dose for patients within any suitable range. For example, insome embodiments, any of the drug products described herein can delivera dose suitable for a pediatric patient (e.g., weighing less than 30 kg)or an adult patient (weighing 30 kg or more).

Although shown as defining a reservoir or chamber (e.g., the chamber125) within which a medicament is directly disposed, in otherembodiments, any of the drug products described herein can include apre-sealed container that contains the medicament, and that is disposedwithin the chamber (e.g., the chamber 125) during manufacturing. In thismanner, the assembly of the upper member and lower member can becompleted in one location and the drug fill/finish operation can beperformed in a different location.

In some embodiments, all or a portion of any of the drug productsdescribed herein can be color-coded for easier identification (e.g.,within hospitals, etc.). In some embodiments, for example, a portion ofeither the upper member (e.g., upper member 150) or the lower member(e.g., lower member 120), or both, or additional parts, can be colored.The coloring can indicate any number of parameters associated with thedrug product, such as, the medicament, the dose (e.g., adult, pediatric,etc.), and/or the expiration date. In other embodiments, the partition(not shown, but described above) can be colored.

In some embodiments, any of the drug products described herein caninclude a partition (or seal) that maintains the medicament within thechamber (e.g., the chamber 125). In some embodiments, the partition canbe coupled to the lower member (e.g., the lower member 120) via a smallspot seal in conjunction with clamping forces produced between the uppermember and the lower member. In use, the spot seals can be configured torupture, break or tear to facilitate removal of the partition frombetween the upper member and the lower member.

In some embodiments, any of the drug products described herein can beincluded within an overwrap (or package) when in its assembled state. Inthis manner, the mouthpiece of the device can be maintained in a sterileenvironment during storage. In some embodiments, an end portion of apartition is coupled to the overwrap such that removal of the overwrapalso removes the partition, thus preparing (or readying) the device foruse.

In some embodiments, a kit includes a medicament delivery device and anapplicator. The medicament delivery device can be any of the medicamentdelivery devices (or drug products) described herein, such as the drugproduct 100 or the drug product 200. The applicator is configured to beremovably coupled to drug product. This arrangement allows a caregiverto position the drug product for use by a user without touching the useror the dry powder inhaler. In this manner, the applicator facilitatesmaintaining sterility during drug delivery. In some embodiments, theapplicator can include an actuator, lever, button, or the like torelease the drug product for use by the patient. In some embodiments,the applicator can contain all or a portion of the drug product (e.g.,the proximal end). In other embodiments, the applicator can be disposedwithin an opening, notch or recess defined by either the upper member orthe lower member of the drug product.

While various embodiments of the invention have been described above, itshould be understood that they have been presented by way of exampleonly, and not limitation. Where methods described above indicate certainevents occurring in certain order, the ordering of certain events may bemodified. Additionally, certain of the events may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above.

For example, although the raised surface 126 is shown as being a flatsurface, in other embodiments, any of the raised surfaces describedherein can have any suitable shape. For example, in some embodiments,any of the raised surfaces described herein can have curved or sphericalsurface. In some embodiments, any of the raised surfaces describedherein can have a conical surface and/or can be raised to terminate in apoint, or be polygonal, ramped or irregular in shape. In otherembodiments, any of the raised surfaces described herein can include aseries of protrusions, posts or extensions that impact the flow aroundand/or through the area of the surface.

Moreover, in some cases, the patient may mistakenly breathe out and intothe inhaler prior to inhalation. In other words, in some cases, thepatient may blow in the reverse direction into the inhaler. In suchcases the raised surface (or plateau), such as for example, the raisedsurface 126, serves as an air deflection surface to deflect the reversedirection air flow to the four air channels (e.g., the channels 160A-Dand openings 163A-D) while powder resides safely in the bottom of thedose chamber. The plateau 126 may be flat as shown in FIG. 13 or convex,concave, ramped or with polygonal surfaces aimed to direct reverse airflow to the four openings 163A-D, for example. This concept may beapplied to inhaler embodiments with two or more air inlets.

In some embodiments, the air inlets and outlets into and out of any ofthe dose chambers described herein (e.g., the dose chamber 125) are bedesigned to disaggregate and deliver all particles of the powdercontained therein. In other embodiments, the air inlets and outlets intoand out of any of the dose chambers described herein (e.g., the dosechamber 125) can be designed to separate particles with the chamberbased on size, mass, geometry, with smaller particles exiting throughthe outlet and predominately larger lactose carrier particles remainingin the dose chamber after dose delivery. Larger lactose carrierparticles with greater mass and centrifugal force flow along the outsidewalls of the chamber, and have sufficient mass and momentum to withstandair inlet flow jets and eddy currents. Thus, such larger particlesremain flowing along the outside walls throughout the inhalation event.Once the inhalation event is complete, the larger lactose particlessettle in the bottom of the dose chamber. The recirculation of theselarger lactose particles and resulting impact forces is important forbreaking the attractive bonds (forces) between drug (API) and lactoseparticles, as well as breaking up agglomerates. In addition, lesslactose or excipient is delivered to the patient which may be beneficialfor dosing regimens involving frequent dosing and high powder loading inthe patient's lungs.

Although various embodiments have been described as having particularfeatures and/or combinations of components, other embodiments arepossible having a combination of any features and/or components from anyof embodiments where appropriate. For example, any of the devices shownand described herein can include any of the ramps, protrusion, or otherflow structures, as described herein. For example, although themedicament delivery device 100 shown in FIGS. 9-10 is not shown asincluding any flow structures (e.g., the ramps 331), in otherembodiments, a medicament delivery device similar to the device 100 caninclude one or more flow ramps, similar to the ramps 331 shown anddescribed above.

Any of the medicament containers described herein can contain any of theepinephrine compositions and/or other drug formulations describedherein.

1. An apparatus, comprising: a first member defining at least a portionof a disaggregation chamber containing a dry powder, the first memberincluding a chamber wall that forms an outer boundary of thedisaggregation chamber; and a second member coupled to the first member,the second member including a surface covering the disaggregationchamber, the second member defining an intake channel and an exitchannel, the exit channel configured to be fluidically coupled to thedisaggregation chamber via an exit opening defined by the surface of thesecond member, the intake channel configured to be fluidically coupledto the disaggregation chamber via an intake port, a center line of aportion of the intake channel being tangential to a portion of thechamber wall of the first member such that a portion of an inlet airflowconveyed into the disaggregation chamber via the intake channel has arotational motion about a center axis of the disaggregation chamber, theintake port defined at least in part by an intake ramp, the intake rampincluding a transition surface that forms an exit angle with respect tothe surface of less than 105 degrees.
 2. The apparatus of claim 1,wherein the transition surface of the intake ramp is parallel to thecenter axis.
 3. (canceled)
 4. The apparatus of claim 1, wherein: thechamber wall is an outer chamber wall surrounding the center axis; andthe first member includes an inner chamber wall that forms an innerboundary of the disaggregation chamber, the inner chamber wallsurrounding the center axis.
 5. (canceled)
 6. The apparatus of claim 4,wherein the inner chamber wall terminates in a raised surface, thecenter axis intersecting the raised surface, the exit opening beingalong the center axis opposite the raised surface.
 7. The apparatus ofclaim 6, wherein the second member includes a protrusion extending fromthe surface, the protrusion in contact with the raised surface tomaintain a distance between the raised surface and the exit opening. 8.The apparatus of claim 7, wherein: the portion of the disaggregationchamber is a first portion; and the surface of the second member definesa second portion of the disaggregation chamber.
 9. The apparatus ofclaim 1, further comprising: a strip disposed between the first memberand the second member, the strip retaining the dry powder within theportion of the disaggregation chamber, the strip fluidically isolatingthe portion of the disaggregation chamber from the intake channel andthe exit channel when the strip is in a first position, the stripconfigured to be moved relative to the first member to a secondposition, the portion of the disaggregation chamber in fluidcommunication with the intake channel and the exit channel when thestrip is in the second position.
 10. (canceled)
 11. The apparatus ofclaim 1, wherein the dry powder includes any one of albuterol sulfate,levalbuterol, ipratropium, albuterol/ipratropium, pirbuterol, orfenoterol.
 12. The apparatus of claim 10, wherein the dry powderincludes a non-sieved lactose excipient.
 13. The apparatus of claim 1,wherein the first member and the second member are monolithicallyconstructed with a living hinge between the first member and the secondmember.
 14. An apparatus, comprising: a first member defining at least aportion of a disaggregation chamber containing a dry powder, the firstmember including a chamber wall that forms an outer boundary of thedisaggregation chamber; and a second member coupled to the first member,the second member including a surface covering the disaggregationchamber, the second member defining an intake channel and an exitchannel, the exit channel fluidically coupled to the disaggregationchamber via an exit opening defined by the surface of the second member,the intake channel configured to be fluidically coupled to thedisaggregation chamber via an intake port, a center line of the intakechannel being tangential to a portion of the chamber wall of the firstmember such that a first portion of an inlet airflow conveyed into thedisaggregation chamber via the intake channel has a rotational motionabout the exit opening, the intake port defined at least in part by anintake ramp, the intake ramp curved outwardly towards the chamber wallsuch that a second portion of the inlet airflow conveyed into thedisaggregation via the intake channel is conveyed towards the chamberwall.
 15. The apparatus of claim 14, wherein: the first portion of theinlet airflow rotates about a center axis; and the intake ramp defines afirst radius of curvature within a first plane normal to the center axisand a second radius of curvature within a second plane normal to thefirst plane, the first radius of curvature and the second radius ofcurvature each opening outwardly towards the chamber wall.
 16. Theapparatus of claim 14, wherein the intake ramp terminates at the surfaceof the second member with an exit angle of less than 105 degrees.17.-22. (canceled)
 23. The apparatus of claim 14, further comprising: astrip disposed between the first member and the second member, the stripretaining the dry powder within the portion of the disaggregationchamber, the strip fluidically isolating the portion of thedisaggregation chamber from the intake channel and the exit channel whenthe strip is in a first position, the strip configured to be movedrelative to the first member to a second position, the portion of thedisaggregation chamber in fluid communication with the intake channeland the exit channel when the strip is in the second position. 24.(canceled)
 25. The apparatus of claim 23, wherein: the second memberincludes a mouthpiece defining a mouthpiece opening in fluidcommunication with the exit channel; the strip includes a pull portionextending beyond the mouthpiece; and the first member and the secondmember define a relief volume that maintains a relief distance betweenthe first member and the second member.
 26. The apparatus of claim 25,wherein at least one of the first member or the second member defines acontact wall that forms a boundary of the relief volume.
 27. Theapparatus of claim 23, wherein: the chamber wall is an outer chamberwall surrounding a center axis about which the first portion of theinlet airflow rotates; the dry powder is formed as a compressed plug;and the first member including a bottom chamber wall that forms a bottomboundary of the disaggregation chamber, the bottom chamber wallincluding a target surface for placement of the compressed plug of thedry powder. 28.-37. (canceled)
 38. An apparatus, comprising: a firstmember defining at least a first portion of a disaggregation chambercontaining a dry powder, the first member including a raised surfacealong a center axis of the disaggregation chamber; a second membercoupled to the first member, the second member including a surfacecovering the disaggregation chamber, the second member defining anintake channel and an exit channel, the intake channel fluidicallycoupled to the disaggregation chamber via an intake port, the exitchannel fluidically coupled to the disaggregation chamber via an exitopening defined by the surface of the second member, the exit openingbeing along the center axis, at least one of the first member or thesecond member including a spacer between the surface of the secondmember and the raised surface of the first member to maintain a distancebetween the raised surface and the exit opening. 39.-40. (canceled) 41.The apparatus of claim 38, wherein: the surface is inner surface; thespacer is a protrusion extending from the inner surface; and the intakechannel fluidically coupled to an external volume outside of thedisaggregation chamber by an external opening defined by an outersurface, the outer surface including a plurality of barrier surfaces atleast partially surrounding the external opening, the plurality ofbarrier surfaces configured to limit obstruction of the externalopening.
 42. The apparatus of claim 41, wherein the intake channelincludes a tortuous path to limit movement of the dry powder from thedisaggregation chamber through the intake channel and the externalopening. 43.-60. (canceled)